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Phentermine is a natural monoamine alkaloid derivative that was initially approved by the United States FDA in 1959 as an anorectic (appetite suppressant) for the treatment of obesity.  It was popularized throughout the early 1970s under the brand name medication “Fastin,” marketed by King Pharmaceuticals.  In the late 1990s phentermine was discontinued from pharmaceutical circulation, but would later reemerge for sale under brand names Adipex-P and Ionamin, as well as generic format.

Pharmacodynamically, phentermine is similar to amphetamine in that it functions as a TAAR1 (trace amine-associated receptor 1) agonist.  The TAAR1 agonism elicited by phentermine facilitates the intraneuronal release of norepinephrine, as well as, to a modest extent, increases intrasynaptic dopamine and serotonin.  Some speculate that phentermine also acts upon VMAT2 (vesicular monoamine transporter 2) to stimulate additional monoaminergic activity.

Based on its mechanism of action, phentermine is referred to interchangeably as a psychostimulant or sympathomimetic.  It helps promote weight loss primarily through the release of norepinephrine within subregions of the hypothalamus (lateral hypothalamic nucleus, arcuate nucleus, ventromedial nucleus), thereby resulting in appetite reduction, fewer food cravings, and increased self-control.  Moreover, phentermine also upregulates peripheral concentrations of norepinephrine and epinephrine to mobilize and break down body fat stores.

Although phentermine is a therapeutically effective weight loss medication when combined with conventional weight management strategies such as caloric restriction, dietary modifications, and physical exercise – it is not devoid of side effects.  Many individuals taking phentermine struggle with unwanted side effects, often to the extent that they may question whether to continue using the medication.  In extreme cases, some individuals will find the side effects of phentermine to be so debilitating, that they discontinue treatment.

Phentermine Side Effects & Adverse Reactions (List)

If you’re taking (or considering) phentermine for weight loss, it is smart to be aware of potential side effects and adverse reactions that may emerge during treatment.  Understand that the specific side effects you experience, as well as the respective severities of those side effects, will be subject to some individual variation.  In other words, the side effects that you experience during treatment with phentermine may differ [perhaps substantially] from those of another user.

Although there’s generally some individual variation in the occurrence of side effects, it is evident that certain phentermine side effects are more commonly reported than others.  Since phentermine is a psychostimulant and increases sympathetic nervous system activation, side effects that commonly occur include: anxiety, dizziness, dry mouth, hypertension, insomnia, and heart palpitations.  Included below is a comprehensive list and discussion of phentermine side effects.

Acne: After taking phentermine for a week or two, you may notice that your skin is suddenly breaking out with acne.  While breaking out with acne is not always caused directly by phentermine, it is likely that the drug can provoke breakouts.  Phentermine activates the body’s stress response, whereby hormone fluctuations occur and in response to these fluctuations, the amount of oil production via the skin increases – increasing likelihood of acne.

Breaking out with acne while taking phentermine may also be related to insufficient intake of various dietary nutrients.  If the drug is suppressing your appetite to the extent that you end up with micronutrient deficiencies, these deficiencies could take a significant toll on your skin health.  To combat the drug-induced acne, you may want to correct all nutrient deficiencies.

Regular skin exfoliation may also prove helpful for reducing acne breakouts.  If the acne is severe, you may find it helpful to consult a dermatologist to determine whether adjunct strategies can be employed to decrease its severity.  Sometimes, no matter what a person does, the acne is so severe that it cannot be controlled.  In this case, it will be up to you to decide whether the benefits you’re getting from the phentermine outweigh the acne.

Agitation: The psychostimulatory effect of phentermine may provoke the side effect of agitation in some users.  Agitation is defined as a state of internal nervous excitement and may be accompanied by restlessness and/or the inability to sit still.  In some cases, agitation will occur only during the first few weeks of phentermine treatment and will subside as a person’s neurobiology adapts to the inflated catecholamine concentrations.

It may be difficult to function if you feel agitated all day, but there may be some things you can to do reduce agitation.  Perhaps the easiest way to reduce agitation is to ensure that you’re not taking too high of a phentermine dose.  Sometimes a simple dosage reduction will be enough to help you lose some weight without causing severe agitation as a side effect.

Agitation is often associated with production of excessive internal energy that isn’t been used.  As a way to cope with the agitation, you may want to get a bit more exercise than usual or remain physically active throughout the day (rather than sedentary).  In addition to getting more exercise as a means for dealing with agitation, some may find it helpful to utilize relaxation techniques each day (e.g. deep breathing) to decrease internal arousal.

Allergic reaction: Adverse allergic reactions to phentermine are uncommon, but not unheard of.  Signs that you may be experiencing an allergic reaction include: swelling of body parts, skin rash/redness, itchiness, dizziness, shortness of breath, and vomiting.  In the event that you notice any possible signs of an allergic reaction, it is imperative that you seek emergency medical care.

An allergic reaction may also be a sign of an interaction between phentermine and another drug.  If you are taking another drug or supplement with phentermine, you may be more likely to experience some sort of allergy.  It also could be that the allergic reaction occurred as a result of using phentermine despite having a medical condition in which its usage is contraindicated.

Any allergic reaction could be fatal or cause damage to your body if left untreated or unaddressed.  Should you experience an allergic reaction, but still want to take a drug for weight loss, your doctor should be able to suggest some viable phentermine alternatives.  There are always other options to consider if phentermine is deemed intolerable.

Anger: Some phentermine users will report that the drug makes them extremely angry, or more prone to anger episodes.  If before taking phentermine you were relatively calm and suddenly transform into the “Incredible Hulk” and every little thing gets you upset, the phentermine is likely to blame.  This drug increases activation of the sympathetic nervous system, priming your body’s freeze-fight-flight response.

Even if you consciously know that you’re not in danger, your nervous system is primed as if you’re in danger.  The combination of the catecholamine release (norepinephrine, epinephrine, and dopamine), as well as upregulation of stress hormones, is enough to make even a Zen master irritable and angry.  If your anger doesn’t seem to improve as you continue treatment, you may want to talk to your doctor about discontinuing the medication altogether.

Feeling angry is not only unpleasant for the individual experiencing this side effect, but acting upon the anger could damage friendships, ruin your reputation, and in extreme cases – get you into legal trouble.  Sometimes a reduction in phentermine dosing may reduce the likelihood of anger, but this is not always effective.  Should you decide to continue with treatment despite the anger you’re experiencing, you may want to ask your doctor about a safe adjunctive agent to help decrease irritability.

Anxiety: Do not be surprised if phentermine causes some anxiety as a side effect, especially when taken at high doses.  The greater the dosage of phentermine you take, the more substantially it activates your sympathetic nervous system via catecholamine release.  This may cause you to exhibit physical symptoms of anxiety and stress such as: chest pain, diarrhea, heart palpitations, and tremor.

Individuals with a preexisting anxiety disorder (e.g. social phobia) are likely at greatest risk of phentermine-induced anxiety due to the fact that most are highly sensitive to changes in catecholamine concentrations.  Slight increases in norepinephrine and dopamine may be enough to trigger a full-blown panic attack in vulnerable individuals.  It could also be speculated that phentermine may exacerbate anxiety by disrupting a person’s circadian rhythm and/or interfering with sleep quality/quantity.

The side effect of anxiety may also be related to phentermine-induced modulation of brain waves, specifically increased beta waves and inhibited alpha waves.  In some cases, relaxation exercises, dosage reduction, and/or safe adjunct anxiolytics may help a user manage anxiety.  However, if the anxiety becomes so extreme that it impairs your ability to function, you may need to quit phentermine.

Blurred vision: Many users of phentermine report visual changes as a side effect.  The most common vision-related side effect is blurred vision.  If your vision becomes blurred during phentermine treatment, it is wise to ask your doctor about potential causes and seek a thorough eye examination from an ophthalmologist.

It has been reported that phentermine may worsen eye pressure among those with glaucoma – thereby damaging eyesight.  In most cases, it is unlikely that phentermine is inflicting direct damage upon your eyesight.  What may be occurring in some individuals is that the drug is increasing sympathetic tone to such an extent, that pupils dilate and blurred vision or “double vision” ensues.

If the blurred vision is resulting from an overactive sympathetic nervous system, decreasing sympathetic activation with relaxation and/or by reducing the dosage of phentermine may be helpful.  Blurred vision could also also be related to signal transmission and/or altered neurochemical activity in visual processing centers of the brain.  For some users blurred vision will subside with continued treatment, but in extreme cases, discontinuation of phentermine may be necessary to restore normative visual perception.

Constipation: A subset of phentermine users document constipation as a side effect of treatment.  The constipation may occur along with other side effects such as bloating and upset stomach, and may be extremely unpleasant to deal with.  In extreme cases, constipation may contribute to hemorrhoids due to the fact that while constipated, users may strain to pass a bowel movement which enlarges rectal veins.

Those experiencing constipation as a side effect of phentermine may benefit from increasing dietary fiber intake, as well as staying hydrated (by drinking more water).  Assuming you’re getting sufficient fiber and are staying hydrated, you may also want to ensure that you’re engaging in some light physical activity (e.g. walking) after each meal.  Remaining sedentary such as lying down after a big meal may increase susceptibility to constipation as a side effect.

Another way to deal with constipation is to take an over-the-counter laxative or fiber supplement.  Ask your doctor whether it would be okay to take an over-the-counter agent to help combat phentermine-related constipation, as well as the particular brand he/she recommends.  If no matter what you do, the constipation fails to subside, it may be wise to stop using phentermine.

Death: In extreme cases, someone may die as a result of using phentermine.  Since phentermine is known to affect heart rate and increase blood pressure, anyone with a history of cardiac events, hypertension, or at risk for cardiac events – should avoid phentermine usage.  Other individuals may be unaware of the fact that phentermine interacts with many other drugs and/or supplements and that interaction effects may increase likelihood of death.

Medical documentation indicates that a subset of phentermine users may experience fatal lung or heart problems.  Your risk of fatality increases if the drug is combined with another appetite suppressant, hence the reason the formerly popular combination known as “Fen-Phen” (Fenfluramine/Phentermine) was discontinued.  Even if you aren’t using other drugs with phentermine, death could occur among a long-term and/or high dose user.

To avoid dying during treatment, discuss all potential contraindications with your doctor and immediately report any adverse reactions that you experience from phentermine.  You may be able to decrease likelihood of death by avoiding long-term and/or high-dose phentermine usage.  It is also a good idea to receive regular medical check-ups to ensure that your heart function, lung function, and blood pressure are healthy during treatment.

Dental problems: Although you may like the weight you’re losing from phentermine, you may dislike the toll it’s taking on your dental health.  Many users, especially those that have taken the drug for a long-term will report that it destroys enamel and causes tooth decay.  The tooth decay and degradation of enamel may occur as a result of another side effect of phentermine known as xerostomia (dry mouth).

Phentermine is known to decrease production of oral saliva, which in turn allows pathogenic bacteria in the mouth to proliferate.  Proliferation of pathogenic bacteria expedites tooth decay and may even cause gum disease.  Additionally, since your saliva contains specialized proteins and minerals that are known to preserve dental health, when salivary production decreases, dental health tends to decline.

Other users may end up experiencing sore teeth, gums, or jaws – as a result of phentermine-induced bruxism (grinding of teeth) and/or jaw clenching.  If you find yourself constantly grinding your teeth, it’s probably because the phentermine has significantly increased your muscle tension.  To avoid serious dental problems during treatment, seek dental evaluation every 6 months.

Depression: A side effect of phentermine that may occur immediately, after a short-term, or over a long-term is depression.  It should be speculated that individuals with an underlying neuropsychiatric disorder may be most likely to experience depression as a side effect of phentermine due to the fact that they may be more sensitive to slight alterations in neurochemistry (e.g. norepinephrine increases).  Depression as a side effect of treatment may signify that you are unable to tolerate elevated norepinephrine and peripheral catecholamine concentrations.

In some cases, depression may result from the fact that the drug kicks their sympathetic nervous system function into overdrive.  This may leave you feeling as if you’re stuck in a chronic state of fight-or-flight with increased anger and irritability – each of which can be associated with depression.  Prolonged activation of the sympathetic nervous system may also detrimentally affect physiology and neurobiology to cause depression by altering: blood flow, gut bacteria, neural activity, and production of neuromodulators (hormones, neurotransmitters, peptides).

In many cases, phentermine users report enhancement of mood during the early weeks of treatment.  This preliminary mood enhancement results from the fact that catecholamine concentrations reach supraphysiological level and stimulate limited numbers of receptors.  However, since the phentermine cannot bypass the evolutionarily hardwired homeostatic feedback loop of the CNS, eventually the “honeymoon phase” of euphoria wears off, receptor densities adjust, and a user may end up depressed.

For those that want to continue using phentermine, it should be advised to work closely with a medical doctor or psychiatrist to adjust dosing to avoid depression.  There may also be safe adjunctive agents that can be prescribed for concomitant use to help stabilize mood during phentermine treatment.  That being said, if the depression you’re experiencing is severe enough to interfere with your lifestyle and/or causes suicidality, it is recommended to seek immediate medical attention.

Difficulty concentrating: While a subset of phentermine users will report that the drug enhances concentration and/or cognitive function, others will find that impairs concentration.  If you find it difficult to concentrate while taking phentermine, it’s likely due to induction of excessive arousal.  Although insufficient arousal can result in brain fog (cloudy thinking) and suboptimal cognitive function, excessive arousal [as may occur from phentermine] can trigger disorganized, rapid, and uncontrollable thinking – making it difficult to concentrate.

Should you find it difficult to concentrate while taking phentermine, you may want to discuss a dosage adjustment with your doctor.  Usually reducing the dosage of phentermine to amount that provides enough stimulation, but not an excessive amount – can facilitate weight loss without impairing your ability to focus.  Engaging in relaxation exercises and/or using a safe anxiolytic may also help optimize your physiological arousal and enhance, rather than impair concentration.

It is also possible that if you have a high homeostatic level of arousal, even the smallest amount of phentermine may impair your concentration.  Perhaps the cumulative neuromodulation exhibited by phentermine such as changes in norepinephrine, dopamine, serotonin, etc. – impair concentration for some more than others.  If impaired concentration is affecting your ability to stay productive at work and/or school – you may want to explore alternative weight loss interventions.

Diarrhea: A common side effect of phentermine is diarrhea or increased frequency of bowel movements.  Phentermine may cause diarrhea in some users by modifying concentrations of specific gut-bacteria, as well as by enhancing gastric motility (movement of food through the digestive tract).  It is likely that in some phentermine users, the laxative effect of diarrhea may be a mechanism by which weight is lost at a rapid pace.

Since diarrhea is an unhealthy way to lose weight, it is recommended to address it as a side effect as soon as it occurs.  Diarrhea may interfere with the body’s ability to absorb dietary nutrients, as well as dehydrate the phentermine user.  If you are experiencing diarrhea, you may want to ask your doctor about using an adjunctive antidiarrheal agent (e.g. Imodium).

You may also want to consider that your current diet may me more to blame for the diarrhea than phentermine.  If you are consuming excessive amounts of fiber and/or aren’t drinking enough water, this could lead you to experience diarrhea.  Furthermore, if you are taking phentermine with a large meal, you may want to try taking it on an empty stomach and waiting several hours after administration before eating – as this may also help with the diarrhea.

On occasion, some individuals will find that the diarrhea is most prominent during the first few weeks of phentermine treatment, but subsides thereafter.  This may be due to a transient adjustment phase in which your gut is adapting to an exogenous substance.  Moreover, you may also want to evaluate whether you may be allergic to any additive ingredients within the coating of your phentermine tablet, as these could also provoke diarrhea in select users.

Dizziness: Among the most common side effects of phentermine is dizziness.  If you feel extremely dizzy and/or as if your head is spinning after each dose – you are not alone.  It is difficult to pinpoint exactly what is causing some individuals to experience dizziness as a side effect, but it may be related to heightened sympathetic nervous activation function as induced by phentermine.

Increased sympathetic nervous system activity constricts blood vessels and modulates cerebral blood flow, each of which could help explain the side effect of dizziness.  Additionally, some individuals taking phentermine may become anxious or stressed from the increased sympathetic nervous system activity – leading them to experience dizziness as a byproduct of the anxiety.  Furthermore, dizziness can occur anytime an individual is adapting to neurochemical changes induced by a drug.

Perhaps the increases in central norepinephrine, epinephrine, dopamine, and serotonin are culprits for bouts of dizziness.  It is also logical to suspect that if phentermine is suppressing appetite significantly and an individual hasn’t eaten for an extended duration, insufficient caloric intake could cause someone to feel dizzier than usual.  Moreover, if a person is suffering from micronutrient deficiencies as a result of phentermine-induced appetite reduction, perhaps these may be causing the dizziness.

To minimize dizziness as a side effect, avoid rapid titrations upward in dosing and/or high doses of phentermine.  Be sure that you’re attaining enough nutrients and ensure that you’re not using another medication and/or substance that may be interacting with phentermine.  For those that cannot cope with the dizziness experienced as a side effect, urgent medical care is advised.

Dry mouth: The dry mouth that occurs during treatment with phentermine may drive you absolutely crazy.  Phentermine is capable of reducing production of saliva by disrupting the salivary glands.  While most people are willing to sacrifice a bit of dry mouth for weight loss, if the dry mouth becomes extreme, it could cause bad breath (halitosis) and tooth decay.

To cope with the dry mouth, you should ensure that you’re drinking sufficient water throughout the day.  You may also want to consider chewing sugar-free gum, as this will help stimulate additional production of saliva.  Avoiding alcohol, caffeine, and tobacco should also be recommended for those with ongoing dry mouth.

To ensure that the dry mouth isn’t taking a significant toll on your dental health, it is recommended to receive regular check-ups from a dental professional.  Some phentermine users experiencing dry mouth may benefit from an over-the-counter saliva substitute and/or mouthwashes specifically formatted for dry mouth.  If the dry mouth doesn’t improve, your breath smells awful, and your teeth are decaying – you may want to reconsider treatment with phentermine.

Euphoria: Many phentermine users report that the drug has a positive effect on their mood, so much so, that they report the side effect of euphoria.  If you feel euphoric during treatment, know that this feeling cannot be sustained over a long-term and is transient.  Euphoria often occurs during the early stages of treatment or in weeks following a dosage increase because the drug stimulates additional catecholamine release.

A greater concentration of norepinephrine, epinephrine, and dopamine stimulate receptor sites – leading users to feel increased pleasure and experience mood enhancement.  The problem is that after awhile, the brain adapts to these increased concentrations and downregulates endogenous production of these chemicals, while also upregulating receptor sites.  This causes the euphoria to eventually subside, especially over a long-term.

Though euphoria is not often considered a problematic side effect, if experienced by an individual with addictive tendencies, they may begin abusing phentermine in effort to maintain this “high.”  For this reason, it is generally smart to report this side effect to your doctor, and realize that it’s unrealistic to maintain this transient blissful state throughout the entire duration of treatment.  Moreover, among those with bipolar disorder, the drug could provoke hypomania or mania – which are problematic.

Frequent urination: A side effect of phentermine reported by numerous users is frequent urination (polyuria).  It isn’t known why phentermine causes frequent urination, but this side effect may be related to drug-induced: anxiety, diuretic effects, and/or thirstiness.  The sympathomimetic effect of phentermine can trigger the fight-flight response and anxiety, which prompts the body to empty urine while fleeing a predator.

The increased fight-flight response activation from phentermine may explain the diuretic effect that users experience.  Also consider that some individuals may become thirsty as a side effect of phentermine and/or drink more water (while eating less) in effort to lose weight.  Drinking a lot of water will certainly increase frequency of urination – and could even result in nocturnal enuresis (bedwetting during sleep).

If you are urinating more frequently than usual during treatment, this side effect should be mentioned to your doctor.  Frequent urination may deplete your body of electrolytes and cause hyponatremia (low sodium).  Efforts should be taken to normalize urinary frequency and restore all electrolytes that were depleted as a result of frequent urination.

Hair loss: A less common adverse reaction to phentermine is hair loss or thinning.  Those that experience hair loss as a side effect of phentermine generally notice it after several months of daily treatment.  It is unknown exactly what causes hair loss (alopecia), but it could be related to a chronically overactive sympathetic nervous system or stress response.

A chronically overactive sympathetic nervous system can trigger alopecia areata in which the body’s immune system attacks hair follicles – resulting in hair loss.  The stress response may also cause telogen effluvium in which large quantities of hair follicles are pushed into a resting phase, and as a result, may fall out upon brushing, combing, or washing your hair.  In most cases, hair loss from phentermine is not permanent and healthy hair is restored within several months of drug discontinuation.

Some have speculated that hair loss from phentermine may be related to a user’s dietary intake and hormone concentrations.  Phentermine may alter production of hormones, which could be the chief culprit for hair loss.  On the other hand, if a person’s appetite is suppressed significantly during treatment to the extent that they are suffering from nutritional deficits – these deficits may be causing the hair loss.

Certain individuals that lose hair during phentermine treatment may find that lowering their dosage decreases the amount of hair loss that occurs, or prevents it altogether.  Others claim that taking specific vitamins and dietary supplements during phentermine treatment may offset drug-induced hair loss.  If the hair loss from phentermine becomes bothersome or extreme, do not hesitate to discuss it with your doctor.

Headaches: Arguably the most frequently reported side effect of phentermine is headache.  Since phentermine is a psychostimulant, it is thought to increase vasoconstriction of intracranial blood vessels, thereby increasing blood pressure – and causing headache.  It also could be that some users end up experiencing such extreme anxiety and/or related muscle tension from increased sympathetic tone, that headaches are triggered.

Another explanation could be that phentermine indirectly increases reactive oxygen species within the brain and/or decreases free-radical scavengers such as superoxide dismutase.  Assuming reactive oxygen species increase and free-radical scavengers decrease in response to phentermine treatment, tension-type headaches may occur as a direct result of elevated reactive oxygen species.  Furthermore, phentermine may have a diuretic effect in some users, causing them to become dehydrated.

If you aren’t drinking enough water and/or restoring other electrolytes (magnesium, sodium, potassium) during treatment, this may also explain the headaches you’re experiencing during treatment.  Sometimes little tweaks in phentermine dosing, drinking plenty of water, and/or adjunctive headache relief agents may be helpful.  However, if headaches are debilitating and interfere with your ability to function, stopping phentermine under medical supervision may be necessary.

Hyperactivity: Some phentermine users may attain such a significant energy boost after each phentermine dose, that they become hyperactive.  If you find that the drug causes hyperactivity as a side effect and you’re unable to sit still, realize that this may interfere with your cognitive function and performance.  It’s difficult to sustain focus on cognitively-demanding academic or occupational tasks if you feel trapped in a state of hyperactivity.

It may be that your current dose is overly stimulating and that your hyperactivity would improve if you reduced the dosage.  However, some individuals will find that even the smallest phentermine dose tweaks their neurochemistry in such a way that they feel overly jittery, stimulated, and hyperactive.  Those experiencing hyperactivity as a side effect may want to consider daily engagement in relaxation exercises (e.g. deep breathing) to reduce arousal and/or using safe adjuvant anxiolytics.

Hypertension: A fairly common side effect reported by phentermine users is hypertension (high blood pressure).  In the event that your blood pressure spikes while taking phentermine, it is important to inform your doctor.  If left untreated, hypertension can cause significant damage throughout the body including: arterial damage, heart damage (e.g. enlargement, disease, failure), brain damage (e.g. stroke), as well as kidney failure.

Phentermine increases blood pressure by stimulating the peripheral catecholamine release including norepinephrine and epinephrine.  The norepinephrine and epinephrine cause vasoconstriction or a reduction in the diameter of blood vessels, thereby increasing the pressure of blood traveling through those blood vessels.  In some cases, hypertension may occur among individuals taking too high of a dose, and a dosage reduction may help mitigate blood pressure spikes.

Since drug-induced hypertension often has no outward symptoms, it is referred to as the “silent killer.  For this reason, all individuals taking phentermine should monitor blood pressure on a daily basis to ensure that it stays within a normative, healthy range.  Moreover, phentermine should never be combined with another psychostimulatory agent, as this may exacerbate the severity of hypertension – possibly leading to a hypertensive crisis.

There may be certain adjunct medications that your doctor could prescribe along with phentermine (e.g. beta blockers) to help keep your blood pressure within a normal range.  However, if your blood pressure is so elevated on phentermine that you need beta blockers to correct it – you may want to work with your doctor to simply discontinue the phentermine.  There are a multitude of other medications that may help you lose weight without taking a toll on your blood pressure.

Insomnia: An extremely common side effect of phentermine is insomnia, or the inability to fall asleep and/or stay asleep at night.  Insomnia may be more likely to occur among phentermine users that are taking a high dose, as the higher dose packs a greater psychostimulatory punch via release of norepinephrine and epinephrine.  That said, in most cases, insomnia experienced as a side effect during treatment may be contingent upon the time at which phentermine was administered.

Since phentermine is thought to last around 10-12 hours for some individuals, should you administer the drug at around 1:00 PM in the afternoon – you’ll likely be wide awake until 1:00 AM.  Even if you try to sleep, it’ll likely be impossible with the supraphysiological concentrations of norepinephrine and epinephrine circulating throughout your central and peripheral nervous system.  A logical strategy for dealing with phentermine-induced insomnia is to administer the drug earlier in the day (e.g. immediately upon waking in the morning).

Early morning phentermine administration should result in the drug “wearing off” in the evening, but not at too late of a time as to interfere with your sleep.  As the effect of phentermine subsides, you may experience an energy crash that times perfectly with your sleep cycle, ultimately allowing you to get a good night’s sleep.  If the insomnia doesn’t improve regardless of administering phentermine earlier, you may want to test whether a dosage reduction would be helpful.

Also consider that phentermine may disrupt your circadian rhythm, as well as cause significant anxiety and/or stress (through its sympathomimetic mechanism) – each of which could prevent you from falling asleep.  Some may benefit from doing something relaxing before bed (e.g. a hot bath with lavender oils) or deep breathing exercises.  If the insomnia becomes severe, usage of an adjuvant hypnotic (sleep inducer) under medical supervision may prove helpful.

Irregular heartbeat: It is possible that you may experience an irregular heartbeat (arrhythmia) as a result of the excessive simulation induced by phentermine.  In the event that you notice an irregular heartbeat during phentermine treatment, it is imperative that you consult a doctor and/or cardiologist to ensure that the drug isn’t putting you at risk for serious cardiac events (e.g. myocardial infarction).  Those with a history of cardiac events are at high risk of experiencing cardiac abnormalities as a result of phentermine, hence reason as to why the drug is contraindicated in these individuals.

A reason as to why phentermine may cause irregular heartbeat has to do with the fact that it constricts peripheral blood vessels.  Constriction of peripheral blood vessels increases blood pressure, which can affect blood flow to the heart, as well as from the heart.  In some cases, an irregular heartbeat could be nothing more than benign palpitations that are often exacerbated by anxiety and/or stress.

However, don’t automatically assume that what you’re experiencing is benign palpitations if you haven’t undergone medical evaluation.  If you received medical checkups and your cardiac function is considered healthy, and you don’t have hypertension, you could be experiencing palpitations.  These palpitations may be corrected by reducing phentermine dosing, taking time to relax each day, and/or using a safe anxiolytic.

Irritability: Phentermine can transform relatively docile, happy-go-lucky individuals into grumpy, vengeful monsters.  The irritability is largely a result of the fact that the drug ramps up sympathetic nervous system function significantly, thereby perpetuating a chronic state of the freeze-fight-flight response.  In other words, a person’s neurobiology and physiology are primed as if they were being hunted by a wild Sabre-tooth tiger – and they cannot snap out of it.

People with chronically high levels of arousal will have a difficult time staving off irritability, and “little things” that previously weren’t bothersome will get on their nerves.  Really the only way to decrease this irritability is to: upregulate parasympathetic nervous system activity, downregulate sympathetic nervous system activity, or simultaneously modulate both.  Likely the most effective method for reducing irritability is to cut back on phentermine dosing.

A lower dose won’t activate the sympathetic nervous system as substantially as a high dose.  If the dosage reduction doesn’t make you less irritable, perhaps your doctor could recommend an adjuvant pharmacological agent or supplement that increases parasympathetic tone to combat irritability.  Should you become so irritable that it’s ruining social relationships such as with coworkers, family, and friends – you may want to consider stopping phentermine altogether.

Itching: Not everyone will experience itching as a side effect of phentermine, but those who do claim that it drives them bananas.  If itching is accompanied by a skin rash, this could be a sign of a serious allergic reaction to phentermine or a potential interaction between phentermine and another medication.  Those who experience itching [especially with a rash] should consult a medical doctor as soon as possible to rule out serious drug-related complications.

Some users have reported that itching didn’t occur during their first few months of treatment, but after the third or fourth month of using phentermine, the itching started.  In this case, it could be that the drug altered a user’s neurobiology and/or physiology over time, in such a way, that a histaminergic response was triggered and the person starts to itch.  Others may not notice round-the-clock itching, but dryness of the skin and/or itching only at a specific time of day (e.g. night).

Since phentermine may be suppressing appetite, it is also reasonable to consider evaluating an individual for micronutrient deficiencies, as certain deficiencies could cause itching and/or a rash.  If you’re scratching your skin incessantly until it bleeds because the phentermine is making you itch, you may want to stop the drug with the help of your doctor.  Upon stopping treatment, the itching should eventually subside (if it was caused by the phentermine).

Some phentermine users theorize that itching could be caused by ingredients within certain preparations of the drug.  There are multiple phentermine manufacturers, and it is possible that in rare cases, one version of phentermine may trigger itchiness whereas another doesn’t.  If you switch to another brand or version of phentermine and the itching abates, chances are it may have been triggered by a minor allergy to a non-active additive.

Libido changes: While taking phentermine, you may notice changes in your libido (sexual desire).  Some users will experience a significant increase in libido, possibly to the extent of phentermine-induced hypersexuality.  It makes sense that a libido spike could occur among phentermine users due to the fact that the drug is stimulating central catecholamine release.

Some individuals really enjoy the bolstered libido as a side effect, whereas others may find a significant libido increase to be distracting.  That said, not everyone taking phentermine reports an increase in sex drive.  Others have reported reductions in libido to the extent that the drug makes them disinterested in sexual pursuits.

A decreased sex drive may be related to the fact that phentermine can cause stress and anxiety.  Excessive stress and anxiety as induced by phentermine may make it difficult for a user to think about and/or enjoy sex, hence the reduced sexual interest.  Sometimes a minor tweak to a user’s dosage (such as an increase and/or decrease) may help correct unwanted libido changes.

If heightened stimulation and/or stress is the root cause of libido changes, a safe anxiolytic may help reverse these changes.  Some users have also reported that the libido changes may be transient and diminish after a week or two of consistent treatment.  All users unhappy with the libido increase or decrease from phentermine should discuss it with a medical professional.

Mood swings: You may notice that phentermine has a significant impact on your mood throughout treatment.  Any drug that tweaks circulating catecholamine levels within the brain and throughout the body – can alter a person’s mood.  Significant shifts in mood may occur during the first few weeks of treatment as a result of your body adjusting to supraphysiological concentrations of stimulatory neurotransmitters.

Initially you may experience some euphoria due to the fact that catecholamine concentrations are elevated and receptor counts haven’t changes.  Over time, you may notice that the euphoria fades, possibly as a result of decreased endogenous catecholamine production and increased receptor counts to deal with the heightened release of norepinephrine.  Eventually a person who was previously euphoric on phentermine could become depressed.

Others may report unpredictable negative mood swings from anger to sadness to anxiety.  These mood swings may not occur “hourly” or overnight, but could for certain individuals.  Anyone with a neuropsychiatric disorder such as bipolar disorder and/or major depression should be carefully monitored if prescribed phentermine.

Muscle cramps: A subset of those taking phentermine will experience muscle cramps as a side effect.  The muscle cramps may be isolated to a particular area of the body such as the back, legs, arms, etc. – or they may occur throughout the entire body simultaneously.  There are several possible ways by which phentermine may be causing you to cramp up during treatment including: dehydration, electrolyte depletion, and/or excessive muscle tension.

In the event that you’re cramping up after taking phentermine, you may want to simply drink more water.  Replenishing water stores is critical, especially among those who experience a drug-induced diuretic effect (and frequent urination).  Also consider that the drug and/or its diuretic effect may be depleting your body of critical electrolytes, and this effect may be amplified if you’re eating less food than usual or losing significant weight.

Ensuring that your body is getting enough potassium, magnesium, calcium, and sodium may improve muscle cramps experienced during treatment.  If your muscles remain cramped despite ramping up water and electrolyte intake, you may want to evaluate whether the drug is increasing your muscle tension.  Since phentermine increases sympathetic nervous system activation, some individuals will notice that the tension within their musculature increases.

To counteract this tension, it may help to engage in relaxation exercises (e.g. acupressure, deep breathing, etc.).  You may also want to determine whether reducing your phentermine dose decreases muscle tension.  If the tension becomes severe and/or painful, your doctor may recommend discontinuing treatment and/or using an adjunctive anxiolytic.

Nausea: When first starting phentermine, many users report severe bouts of nausea.  The nausea you experience as a side effect may be accompanied by lightheadedness, vomiting, and/or dizziness.  Some users will find that the nausea only lasts for a week or two and subsides once the body has fully adapted to the ongoing administration of phentermine.

In many cases, nausea may be a result of insufficient caloric intake and/or lack of dietary nutrients.  If you are intentionally starving yourself, exercising excessively, and/or are deficient in nutrients – nausea may emerge during treatment.  To combat nausea while taking phentermine, ensure that you’re eating enough food, aren’t over-exercising, and that all nutrient deficiencies are corrected.

Nausea could also be caused by gastrointestinal irritation associated with taking phentermine on an empty stomach.  If you feel nauseous each time you take phentermine without food, you may want to try taking it with a meal and/or light snack to determine whether the nausea subsides.  In other cases, nausea could be a sign of an interaction with another substance you’ve taken, an allergic reaction to phentermine itself, or perhaps related to drug-induced anxiety.

A medical doctor should be able to help you determine why phentermine is causing you to feel nauseous, as well as figure out how to attenuate this nausea.  Ways to deal with nausea may include: dosage reduction, food consumption, and/or using an antiemetic agent.  That said, if the nausea is intense and causes you to vomit on a daily basis, phentermine discontinuation will be necessary.

Palpitations: While using phentermine, you may experience palpitations as a side effect.  Palpitations are defined as noticeably irregular, rapid, or strong heart beats as a result of agitation or exertion.  If you’ve never experienced palpitations before, they may take you by surprise, leading you to mistakenly assume that you’re about to have a heart attack or that your heart is somehow damaged.

As was mentioned earlier, any heart rhythm irregularities experienced during phentermine treatment should be evaluated by a cardiologist.  If the cardiologist suggests that you aren’t at risk for adverse cardiac events, the irregular heartbeats you’re experiencing are likely a benign palpitation.  Nonetheless, these palpitations may significantly increase your anxiety level due to the fact that they feel highly uncomfortable.

To reduce likelihood of palpitations, decreasing phentermine dosing is a viable option, as this will reduce sympathetic output.  The greater the dose of phentermine you’re taking, the higher your arousal will be, resulting in vasoconstriction of peripheral blood vessels, increased blood pressure, as well as altered inflow and outflow of blood to your heart.  Alterations in blood flow may explain some palpitations you experience.

Nevertheless, palpitations can create a vicious circle in that while they’re experienced, a user may feel highly anxious.  This spike in anxiety may reinforce the future occurrence of palpitations, resulting in more palpitations and anxiety.  To cope with palpitations as a side effect, it is recommended to accept that they may occur rather than attempting to resist or “fight” them, and consider a safe adjunct anxiolytic to enhance parasympathetic tone.

Restlessness: It is not uncommon for phentermine to increase mental and physical stimulation to such an extent, that users are unable to sit still or remain calm.  Restlessness is a common side effect of phentermine and is likely a result of the fact that the drug increases mental and physical arousal.  This may lead you to feel as if you have too much energy for your own good, especially in settings such as at work or school.

This restlessness is synonymous with hyperactivity and is characterized by hyperarousal.  To decrease the restlessness, it is necessary to combat the hyperarousal.  Some ways by which a person may be able to decrease their restlessness include: getting plenty of physical activity throughout the day (to burn some energy), practicing relaxation exercises to increase parasympathetic function, and/or by using calming essential oils (such as lavender).

Another logical strategy is to decrease phentermine dosing or work with your doctor to find a safe adjuvant substance that enhances relaxation.  Keep in mind that those with an already-anxious predisposition may become restless even at low doses of phentermine.  Should restlessness interfere with your ability to remain calm, focused, and productive – you may need to cease phentermine usage.

Sexual dysfunction: As was already discussed, phentermine can modulate a user’s libido – sometimes to a significant degree.  Though a libido increase or decrease may occur in many users, some men will experience impotence (erectile dysfunction) as a side effect.  It isn’t known what causes the erectile dysfunction, but some speculate that excess sympathetic tone can interfere with the ability to maintain an erection.

Among the men that experience erectile dysfunction as a side effect of phentermine, some claim that it diminishes within several weeks of treatment.  Even more disconcerting may be the fact that phentermine can temporarily cause shrinkage of the genitals – possibly resulting in some embarrassment.  Both men and women using phentermine may experience anorgasmia or the inability to orgasm as a result of an overactive sympathetic nervous system.

To reduce likelihood of erectile dysfunction and/or anorgasmia, users may want to try decreasing their phentermine dose. Getting enough sleep, keeping stress to a minimum, and consuming sufficient nutrients may be helpful for reversing drug-induced sexual dysfunction. If the sexual dysfunction isn’t extreme, you may be willing to put up with it as a side effect as long as weight loss continues.

Skin rash: A skin rash as a result of phentermine should be promptly evaluated by a medical professional.  Any skin rash may be a sign that you’re allergic to phentermine, especially if the rash is accompanied by swelling, itchiness, dizziness, nausea, and/or vomiting.  Skin rashes may appear isolated to one specific area of the body such as your stomach, or may be widespread across multiple regions of the body.

Some individuals will notice red blotches across their skin, whereas others may notice raised bumps.  If the rash itches, chances are that it’s triggering the release of histamine in the brain, signaling that the body is unable to tolerate phentermine.  A skin rash could also occur as a result of hormonal changes that occur during phentermine treatment, ultimately causing dry skin.

Moreover, decreased caloric intake may result in nutrient deficiencies that lead some individuals to develop a rash.  Be sure that your hormones stay within a healthy range and that you are still eating a nutrient-dense diet while taking phentermine to avoid skin abnormalities.  If the rash persists and a doctor believes it was caused by phentermine, you’ll need to discontinue the medication and opt for an alternative.

Sleep disturbances: Most people that have used high doses of phentermine and/or administered the drug too late in the day, will experience some sleep problems.  Since the drug significantly increases sympathetic tone, it should be suspected that this may interfere with your sleep quality by inhibiting your brain’s ability to enter the deepest stages of sleep (characterized by delta waves).  Phentermine may also disrupt your sleep as a result of provoking the side effect of anxiety.

If you experience severe physical and/or psychological symptoms of anxiety as a side effect of phentermine such as: rapid thinking, heart palpitations, sweating, etc. – you may have a tough time falling asleep and staying asleep throughout the night.  Furthermore, some users have reported experiencing crazy dreams, vivid dreams, and/or nightmares that wake them up in the middle of the night and significantly disturb their sleep.  It is also logical to suspect that phentermine may disrupt your body’s circadian rhythm, resulting in poorer sleep quality and reduced sleep quantity than usual.

For a lucky subset of phentermine users, the sleep disturbances will diminish after several weeks of treatment as their body adapts to the drug.  If you constantly wake up feeling groggy or as if you got a horrible night’s sleep throughout your treatment, it may be helpful to consult both your doctor and a sleep specialist.  A sleep specialist should be able to compare your sleep architecture before treatment and during treatment with phentermine and explain whether any deleterious changes have occurred.

It may be tough to deal with sleep disturbances, especially if they are impairing your ability to function throughout the day.  To combat these disturbances, it may be helpful to decrease dosing or take phentermine very early in the morning so that it’s stimulatory effect subsides by the evening, allowing you to get some deeper sleep.  You may also want to ask your doctor whether he/she would recommend an adjunct sleep aid to attenuate your phentermine-induced sleep disturbances.

Suicidal thoughts: A rare adverse reaction to phentermine that some individuals may experience is suicidal thoughts.  In the even that you feel suicidal and/or as though you want to die while taking phentermine, it is necessary to seek emergency medical attention.  It may be helpful to understand that any drug altering your neurochemistry can deleteriously affect your mood, perception, and trigger suicidal thoughts.

Phentermine modulates neurotransmitters such as norepinephrine, epinephrine, dopamine, serotonin – each of which can affect mood.  Although the modulation of these neurotransmitters may be tolerated well by certain individuals, others may end up feeling suicidal.  Users with neuropsychiatric disorders such as major depression should be carefully monitored while taking phentermine.

Furthermore, anyone abusing phentermine such as by taking supratherapeutic doses may be at risk for suicidal thoughts, possibly accompanied by drug-induced psychosis (hallucinations, delusions, etc.).  In other cases, suicidal thoughts may be experienced between phentermine doses (such as when it wears off) due to downregulation in endogenous catecholamine production.  Anyone experiencing suicidal thoughts should work closely with a medical professional to correct drug-induced neurochemical imbalances.

Sweating: Some people taking phentermine may notice the side effect of hyperhidrosis (excessive sweat production).  In rare cases, the extreme sweating may be caused by an allergic reaction to phentermine, but in most cases it is likely caused by an increase in sympathetic nervous system function.  When phentermine induces catecholamine release, the freeze-fight-flight response is activated and the body begins mobilizing additional energy stores.

Upon mobilization of these energy stores, a person’s arousal and heart rate increases and they are ready to outwit an attacking predator with this additional energy.  Most sweating that occurs is a result of the body attempting to keep you cool from the additional energy being produced by the sympathetic nervous system.  Without sweat production, the body would overheat and anyone in a dangerous situation would incur damage from this overheating.

Just know that when taking high doses of phentermine, it may be impossible to avoid sweating more than usual.  Those that have a history of anxiety disorders and/or untreated anxiety may sweat a lot at low doses due to the fact that their sympathetic tone is already heightened from anxiety.  You may notice that your palms feel clammy, your work clothes are always drenched in sweat, and/or your bed sheets are soaked each morning upon waking.

For some individuals, sweating may be more noticeable at a particular time of the day (e.g. morning), whereas for others it may occur throughout the entire day.  Should you notice increased sweating, your best bet is to keep your body in a cool environment.  You may also want to engage in some sort of relaxation exercise and talk to your doctor about a potential reduction in your phentermine dose.  Dosage reduction and/or relaxation should enhance your parasympathetic tone and may help reduce the severity of hyperhidrosis.

Taste changes: A side effect of phentermine that many individuals find annoying is dysgeusia or distortion in the perception of taste.  It is unclear as to how phentermine causes distorted taste perception, but some speculate that it may be related to the common side effect of xerostomia (dry mouth).  Dryness within the mouth is understood to affect taste, especially in the event that it is extreme.

Others speculate that phentermine may interfere with a person’s taste buds and/or sense of smell.  This interference may alter taste signaling transmitted to sensory processing centers within the brain, causing a user to perceive the taste of delicious foods as “bland” or even “disgusting.”  The severity of dysgeusia may be subject to variation based on the particular user – some may find it to be tolerable, whereas others will discontinue treatment if a drug significantly affects their taste.

While distorted taste may make it easier to lose weight on phentermine due to the fact that it decreases the pleasure/reward derived from food consumption, it may also lead some individuals to become depressed.  Others may report experiencing ageusia (complete lack of taste), hypogeusia (reduction in taste sensitivity), or notice a metallic taste in the mouth.  Anyone who experiences major taste changes should consult a medical professional to ensure that phentermine is the cause and not another serious medical condition.

Decreasing the dosage of phentermine may prove helpful for restoring taste of some users, but not all.  It should also be considered that if phentermine suppresses your appetite to such an extent that you aren’t meeting recommended daily allowances of dietary micronutrients, deficiencies of micronutrients (such as zinc and niacin) may be the culprit for your taste changes.  Ensuring that you’re eating a nutrient-dense diet and aren’t deficient in zinc and/or niacin may be an effective way to prevent taste changes.  Others have reported that artificial saliva and alpha lipoic acid may be useful in reducing dysgeusia from phentermine.

Thirstiness: Increased thirst or excessive thirstiness has been reported as a side effect of phentermine.  Though it is recommended to stay hydrated throughout treatment by drinking plenty of water, thirstiness may lead to excessive water consumption which can be dangerous.  It is possible that some users may end up with water intoxication or water poisoning as as a result of their increased thirstiness.

Drinking too much water is known to disrupt the balance of electrolytes within the body and is associated with hyponatremia (insufficient sodium within the bloodstream).  Thirstiness can also be a symptom of various medical conditions such as diabetes.  Should you experience heightened thirst while taking phentermine, discuss it with a medical professional.

The excessive thirst may subside with continued treatment, but if it doesn’t, be sure that your electrolytes are kept within a normal range and that you aren’t at risk for water intoxication.  Some have reported that drinking too much water can also lead them to feel nauseous, dizzy, and downright sick.  If the thirstiness is uncontrollable and/or interfering with your ability to function – you may want to stop phentermine.

Tremors: Phentermine can often generate such a potent psychostimulatory effect that users end up experiencing tremors (shakes) as a side effect.  The reason tremors occur is due to the fact that the drug significantly increases catecholamine levels both centrally and peripherally.  This primes the body for action and mobilizes energy stores, leaving a user feeling highly stimulated –perhaps causing them to shake uncontrollably.

You may notice tremors in a particular area of your body such as the arms, hands, or legs.  The tremors may be most likely to occur among those taking high doses of phentermine, and less likely among low dose users.  At high doses, a person’s physiology is stimulated more significantly as a result of additional catecholamine release – making it difficult to avoid a phentermine-induced tremor.

For this reason, if you are experiencing disconcerting tremors your doctor will likely recommend decreasing your phentermine dosage.  Keep in mind that synergistic factors such as anxiety or concurrent usage of psychostimulants (e.g. caffeine) may increase likelihood of tremors even at standard doses of phentermine.  Also realize that tremors may be more likely to occur among those that have only used phentermine for a short duration and may subside with continued treatment.

Vomiting: An unlucky subset of phentermine users will end up vomiting as a side effect.  The vomiting is generally preceded by other symptoms such as nausea, dizziness, and lightheadedness – and may be more likely to occur during the first few weeks of phentermine treatment.  Vomiting is an adverse reaction often signifying that a person initiated treatment at too high of a dosage.

Those who start with a very low phentermine dose and titrate upwards slowly (over a period of weeks or months) will give their body time to adapt to the drug, possibly decreasing likelihood of vomiting.  That said, vomiting could also be a sign that you’re allergic to phentermine, especially if accompanied by other symptoms such as swelling and a skin rash.  Anyone who experiences vomiting as a side effect should seek immediate medical care to rule out more serious causes.

Since vomiting can deplete your body of nutrients and cause dehydration, it is important to ensure that you stay hydrated and consume nutrient-dense foods as soon as you’re able to keep them down [after vomiting].  It is possible that vomiting may also be induced by gastrointestinal irritation resulting from taking the drug on an empty stomach.  You may want to experiment whether taking the drug with or without food may decrease vomiting.

Some phentermine users consider it normal to vomit within the first few weeks of treatment, and note that the effect eventually subsides.  Those who vomit may want to consider an adjunctive antiemetic agent along with a dose reduction to determine whether it subsides.  Should you continue to vomit throughout treatment, it may be a sign that phentermine isn’t compatible with your body and discontinuation may be necessary.

Note: If you have any questions or concerns about a specific phentermine side effect, it is recommended to seek immediate medical attention.  A medical professional will help determine whether any reactions you’re experiencing are harmful/dangerous.  Moreover, professionals should be able to come up with some safe strategies for dealing with unwanted side effects.

  • Source: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011706/

Variables that influence Phentermine side effects

When assessing the side effects that you’re experiencing (or are likely to experience) during treatment with phentermine, it may help to understand some influential variables.  These variables dictate the specific side effects that you experience, as well as their respective severities.  Examples of such influential variables include: phentermine dosage, co-administered substances, cumulative term of administration, and various individual factors (e.g. administration parameters, comorbid medical conditions, hepatic metabolism, stress level, etc.).

  1. Dosage (High vs. Low)

In general, individuals taking a high dose of phentermine are likely to experience a greater number of side effects, as well as more severe side effects – than those taking a low dose.  This is due to the fact that when taken at a high dose, a larger quantity of the phentermine chemical is ingested.  A larger amount of the chemical ingested means that the drug will exert a more substantial effect upon a user’s neurochemistry and physiology.

Knowing the mechanism of action associated with phentermine, we can predict that central and peripheral norepinephrine release will be greater after ingestion of a 37.5 mg dose than a 15 mg dose.  As a result of this heightened norepinephrine release after taking the 37.5 mg dose compared to the 15 mg dose, side effects are more likely to occur.  Not only are side effects more likely to occur, but they are likely to be more pronounced in terms of severity.

This is because the greater the amount of phentermine administered, the more significant the psychostimulatory effect.  You may notice that at low doses, side effects such as agitation, anxiety, and/or insomnia are relatively negligible or manageable – whereas when your dose increases, you may struggle to tolerate them.  Not only are side effects more likely to occur from higher doses of phentermine as a result of the heightened stimulatory effect, they may occur as a result of an increased pharmacokinetic burden.

In other words, when you take a high dose of phentermine, your body may metabolize, distribute, and eliminate it less efficiently than it would a lower dose.  The less efficient pharmacokinetics may provoke certain side effects after taking a high dose that wouldn’t have occurred at a low dose.  You may also want to reflect upon the fact that a subset of dosage-related side effects may be related to your body attempting to maintain homeostasis.

Whenever ingesting an exogenous substance such as phentermine, it disrupts homeostatic processes within your brain and body.  At lower doses, the disruptions in homeostatic processes are less significant, meaning there’s less of a backlash from your body against the drug.  At high doses, your internal homeostatic processes are disrupted to a greater extent, meaning the backlash from your body against the drug may be more significant.

As an example, let’s say the drug mobilizes a moderate amount energy stores at a low dose, disrupting homeostatic body temperature by causing an increase.  In effort to maintain homeostasis, your body responds by increasing production of sweat – which keeps you cool.  However, at a high dose of phentermine, more energy stores may be mobilized, causing your temperature to increase more significantly than at a lower dose.

In effort to maintain homeostasis after the high dose, your body may generate significantly more sweat [compared to the low dose].  In brief, most users will notice that the number and severity of side effects from phentermine are contingent upon the dosage that they take.  If you take a low dose, expect fewer side effects than if you’re taking the highest possible dose or a supratherapeutic dose (e.g. 37.5+ mg per day).

  1. Co-administered substances

If you’re taking phentermine, it is important to be aware of the fact that any co-administered substances you regularly use may have an impact on the side effects you’re experiencing from phentermine.  Many substances are contraindicated for usage with phentermine, and if you’re using a contraindicated substance, you will be at increased risk for serious adverse reactions.  For this reason, it is always important to confirm with your doctor that co-administered substances you’re using are safe with phentermine.

Some notable contraindications include: stimulatory agents (e.g. NDRIs, DRIs, NRIs), monoamine modulators (e.g. MAOIs, SNRIs, SSRIs, TCAs), as well as drugs that increase blood pressure.  For example, it is known that taking fenfluramine along with phentermine (a combination previously marketed as “Fen-Phen”) amplifies risk of serious adverse cardiac events and lung damage.  Assuming you aren’t using a substance that’s medically contraindicated with phentermine, there’s still a possibility of an interaction.

Many substances that aren’t formally contraindicated with phentermine could still interact with it pharmacokinetically to alter side effects.  Although phentermine isn’t extensively metabolized through the liver, a percentage of each dose undergoes hepatic metabolism by way of the CYP3A4 isoenzyme.  Therefore, we should expect that any drug taken along with phentermine that either inhibits OR induces CYP3A4 isoenzyme function may influence side effects experienced.

If a CYP3A4 inhibitor were to be administered along with phentermine, individuals may experience an increase in side effects due to prolonged phentermine metabolism.  Some examples of potent CYP3A4 inhibitors include:  Chloramphenicol, Clarithromycin, Cobicistat, Ketoconazole, and Ritonavir.  Oppositely, those who take a CYP3A4 inducer along with phentermine may incur side effects related to expedited phentermine metabolism.

Examples of some CYP3A4 inducers include: Butalbital, Capsaicin, Carbamazepine, Modafinil, Phenytoin, Rifampicin, and St. John’s wort.  The degree to which metabolism is altered (expedited or prolonged) will be contingent upon the dosage of the CYP3A4 inducer or inhibitor – the larger the dosage, the more significant the side effects are likely to be.  Also realize that certain drugs such as carbonic anhydrase inhibitors (e.g. acetazolamide) are known to decrease phentermine elimination, possibly influencing side effect occurrence.

Another set of co-administered substances will not be contraindicated, nor will they interact with phentermine by altering its pharmacokinetics – but will still impact the occurrence of side effects.  As an example, co-administration of a substance with stimulatory properties (e.g. caffeine) may exacerbate side effects such as anxiety, insomnia, palpitations, tremor, etc.  On the other hand, co-administration of a substance with anxiolytic properties may buffer against the occurrence of certain side effects (e.g. anxiety, insomnia, etc.).

For this reason, you may want to evaluate whether any co-administered substances you’re using could be amplifying side effects via a synergistic stimulatory effect OR whether co-administered substances you’re taking may be covering up side effects from phentermine that you would’ve otherwise experienced.  Also consider that you may be mistakenly attributing side effects to phentermine that are really a side effect of another agent.  Moreover, understand that phentermine could decrease the efficacy of certain co-administered medications – possibly leading to symptomatic resurgence of a medical condition.

  1. Term of administration

The cumulative duration over which you’ve been taking phentermine may dictate the side effects that you experience.  A person that’s only taken phentermine for a few weeks may experience a different set of side effects than an individual that’s been using phentermine for a few months.  Although phentermine is only recommended for short-term usage, a person that’s been taking phentermine for multiple years (a long-term) may experience notably different side effects than short-term and moderate-term users.

Short-term: If you’ve only been using phentermine for a short-term such as several days or weeks, side effects are likely to occur primarily due to the fact that your brain and body haven’t adjusted to receiving the drug.  This lack of adjustment will trigger side effects that will eventually subside with continued usage.  Those new to phentermine often report side effects such as nausea, vomiting, and sexual dysfunction – but note that they go away with continued usage.

Another reason side effects may occur over a short-term is related to the fact that users haven’t fully optimized their dosing.  A new phentermine user may begin treatment with the highest possible dose and fail to realize that this may be too much of the drug for their body to handle.  Eventually, as treatment is continued and a doctor reconfigures the dosing (via a reduction), side effects lessen.

That said, some users may use an extremely low dose of phentermine over the short-term due to lack of tolerance.  Based on the low dose of phentermine utilized over a short-term, side effects may be more tolerable.  Side effects may be more likely to worsen for some over a moderate-term or long-term due to tolerance and corresponding dosage increases.

Moderate-term: Those that have been taking phentermine for several months will have likely adapted (neurobiologically) to its regular administration, and will no longer experience adjustment-related side effects.  Moderate-term users are also likely to have properly configured their dosage such as by decreasing too high of a dose.  For this reason, we should expect fewer total side effects among moderate-term users compared to short-term users.

However, it could be that a short-term user may have begun treatment on an extremely low dose and titrated his/her dose upwards after a month or two of treatment.  This upward titration may result in side effects related to the increase in dosing.  Furthermore, it is reasonable to suspect that after several months of regular phentermine administration, cumulative changes to an individual’s neurobiology have accrued – some of which may be setting the stage for deleterious long-term effects.

Long-term: A person that’s taken phentermine for a long-term may be less likely to experience side effects than short-term and/or moderate-term users for a couple reasons.  The first reason side effects are less likely among long-term users is that the neurobiology of the long-term user will have long been acclimated to phentermine’s presence.  As a result of this extensive term for acclimation, no adaptation-related side effects will still be occurring after a long-term.

The second reason side effects are less likely to occur among long-term users is related to the fact that a long-term user will have likely optimized his/her dosage.  Optimization of dosing minimizes the likelihood that a user is taking too high of a dose or a dose that causes significant unwanted side effects.  Despite the fact that some long-term users may be less likely to experience side effects – other long-term users may notice more numerous and/or severe side effects.

More numerous and/or severe side effects over a long-term is related to the fact that daily administration of phentermine can take a cumulative toll on a person’s neurobiology and physiology.  In other words, the chronic sympathetic activation may be slowly taxing the heart, lungs, kidneys, etc. – resulting in serious long-term effects or damage.  Moreover, long-term users are more likely to have built up a tolerance to lower doses, and may be taking a high or supratherapeutic dose whereby more side effects are triggered.

  1. Individual factors

In addition to dosage, co-administered substances, and duration of administration – it is necessary to consider that individual factors may play a significant role in the incidence of side effects.  Two individuals could take 37.5 mg phentermine for the same duration without any co-administered agents, yet one may experience notably different side effects than the other.  Hypothetically speaking, one of the aforementioned users may experience severe dizziness, insomnia, libido decrease – as side effects, yet the other user may report headaches and a libido increase.

Since the two users are taking the same phentermine dose (37.5 mg), and have been using it for the same duration without any other substances, we would speculate the side effects are likely to be similar – yet they are not.  So what explains the differences in side effects between the two individuals?  Individual factors.  Examples of individual factors that influence phentermine side effects include: administration parameters, age, genetics, medical conditions, sleep (quality/quantity), and stress – that often provoked

Administration parameters:  The time of day at which you administer phentermine, as well as whether you take it with or without food – can influence side effects that you experience.  A person who administers phentermine in the afternoon or early evening may struggle with insomnia and/or sleep disturbances due to the fact that drug is still exerting a stimulatory effect.  On the other hand, someone taking phentermine in the early morning may be able to avoid insomnia and/or sleep disturbances because its effect will have diminished by the evening.

Most individuals will notice more or less debilitating side effects based on the time of administration in relationship to the user’s circadian rhythm.  A time of administration that doesn’t significantly disrupt the circadian rhythm will likely provoke fewer side effects than an administration time that interferes with the circadian rhythm.  Some side effects may be more likely to occur and/or more severe depending on whether phentermine was ingested on an empty stomach or after a meal.

Taking phentermine on an empty stomach may cause side effects such as GI distress and nausea that wouldn’t have occurred had the drug been taken with food.  Others may have an unfavorable experience if phentermine is taken after a meal or with food, possibly leading them to experience diarrhea or vomiting.  It should also be considered that the amount of time prior to food consumption either before or after phentermine administration, and possibly the specific type of food consumed along with phentermine – may have an impact upon side effects.

Age: A person’s age may make them more or less susceptible to phentermine side effects.  Healthy adults are least likely to experience side effects compared to pediatrics and elderly patients.  This is due to the fact that a healthy adult has a fully developed brain and body, and organ function hasn’t deteriorated as a result of old age.

A pediatric user may be less equipped to handle standard doses of phentermine due to the fact that his/her body and brain aren’t fully developed.  Additionally, pediatrics are generally smaller than adult counterparts, making standard doses more potent – and more likely to trigger side effects.  Elderly individuals may be at increased risk for adverse events while using phentermine due to age-related medical conditions, adjunctive drug usage, and declining organ function.

Body attributes: A person’s physical attributes including body size (height / weight), as well as body composition (fat / muscle) could influence phentermine side effects.  In general, it is thought that a larger individual is capable of efficiently handling a greater amount of the drug than a smaller individual.  Assuming a person who’s 6’6” and 400 lbs. took phentermine at a dose of 37.5 mg, the effect of the drug may be less significant due to his/her size than a user who’s just 4’4” 300 lbs.

The percentage of an individual’s fat and muscle may also influence side effects based on whether the drug is fat-soluble (lipophilic) or water-soluble (hydrophilic).  A phentermine user with significant muscle mass may retain the drug for a shorter or longer duration than a person with minimal muscle – due to the fact that the muscle increases water retention.  Although the impact of fat and muscle percentage upon side effects is likely to be negligible (and unnoticeable), it should be taken into consideration.

Dietary intake: A phentermine user’s dietary intake could have an influence upon side effects.  Someone who doesn’t eat a nutrient-dense diet and skips many meals may suffer from micronutrient deficiencies.  These micronutrient deficiencies may exacerbate certain side effects of phentermine such as: anxiety, mood swings, insomnia, etc.  A person who’s getting sufficient nutrients from his/her diet may find that adequate nutrition acts as a safeguard against side effects.

You may also want to consider the amount of time you’re in a fasted state compared to a fed state.  Though phentermine helps people lose weight by reducing appetite and burning fat stores, if appetite reduction is extreme and a person is in a prolonged fasted state – the fasting alone could cause a host of unwanted side effects.  Those eating enough overall food (without going overboard) should have best results in terms of weight loss and side effects with phentermine.

Exercise: How often are you exercising during treatment and what time of day do you exercise?  Have you thought about the fact that your exercise regimen may be increasing or decreasing drug-related side effects?  Someone who experiences insomnia from phentermine may not realize that the insomnia is worsened with exercise within an hour or two of bed.

On the other hand, another user who initially experienced insomnia with phentermine may notice that when they get more exercise early in the day – they no longer experience insomnia.  The type of exercise that you utilize to stay in shape should be evaluated for safety while using phentermine.  For example, running sprints while taking high doses of phentermine may be more likely to cause serious adverse cardiac events (e.g. myocardial infarction) than going for a walk.

Genetics / Epigenetics: Your genetics and epigenetics are likely responsible for some side effects that you experience during treatment.  There are now genetic testing services available such as GeneSight that can be used to determine whether you’re likely to find a drug tolerable or intolerable.  The CYP3A4 gene which encodes for the expression of the CYP3A4 isoenzyme, can influence the metabolism speed of phentermine, which in turn can influence side effects.

Even genes that aren’t implicated in pharmacokinetic processes such as metabolism likely will determine how well you can handle phentermine.  Someone with genetic polymorphisms that affect the NET transporter may result in an increase or decrease of side effects from phentermine.  Even genes that scientists haven’t discovered to affect phentermine tolerability may determine certain side effects.

It should also be noted that a person’s epigenetic signature (gene activity in response to environment) could alter the tolerability of certain phentermine side effects.  If we were to take 2 identical twins, yet place one in a stressful environment in the South and another in a calm environment in the North – side effects of phentermine may differ based on specific epigenetic expression in reaction to environment.  Don’t discount the role of epigenetics in drug tolerability and side effects.

Medical conditions: If you have a medical condition, understand that usage of phentermine may be contraindicated.  Furthermore, if you are at risk for any medical conditions, taking phentermine may provoke or exacerbate certain side effects that wouldn’t have occurred if you weren’t at risk.  Individuals without any comorbid medical conditions should be less likely to experience side effects than those with medical comorbidities.

Those with medical comorbidities are likely to experience an overlap of phentermine side effects and symptoms of their particular condition.  They are also likely to experience some interaction effects between phentermine and medications used to treat comorbid conditions.  Phentermine usage is contraindicated among those with conditions such as: atherosclerosis, diabetes, epilepsy, glaucoma, heart disease, hypertension, hyperthyroidism – as well as various others.

Anyone who is hypersensitive to sympathomimetic amine, pregnant or nursing, and/or with a neuropsychiatric disorder (e.g. bipolar disorder) – should avoid phentermine usage.  Always double-check with a licensed medical professional to ensure that phentermine is safe given your current medical status.  Furthermore, even if it is “safe” to take phentermine with a particular condition, realize that you may be more vulnerable to certain side effects than healthy users.

Sleep & Stress: The amount/quality of sleep that you’re getting while taking phentermine can make you more or less likely to get certain side effects.  Someone that’s managing to get 8 to 10 hours of quality sleep per night may be at less risk of side effects than a person who’s only able to get 4 to 8 hours of disrupted sleep.  If you’re getting a good night’s sleep, your neurobiology and physiology will differ from a person that’s not getting enough sleep.

The individual with poor sleep may exhibit suboptimal levels of hormones, neurotransmitters, and maladaptive brain activation – making him/her more vulnerable and/or less able to cope with phentermine side effects.  A person with quality sleep should exhibit favorable concentrations of hormones and neurotransmitters – possibly increasing his/her ability to cope with side effects and/or decreasing likelihood that they’ll occur.  Stress should also be factored in as an influencer of side effects in that high stress is likely to decrease ability to tolerate phentermine.

Phentermine: Do the benefits outweigh the side effects?

If you’re taking phentermine, you’ll want to conduct an ongoing cost-benefit analysis to determine whether the therapeutic weight loss effect outweighs the side effects that you experience.  A lucky subset of individuals taking phentermine will end up losing significant weight during treatment and tolerate the drug extremely well without any unwanted side effects.  If you are fortunate enough to experience all benefits and no unwanted side effects, it makes logical sense to continue treatment.

Other individuals may take phentermine and experience no significant side effects, but find that it doesn’t really help with weight loss efforts.  If you’ve been taking phentermine for months and haven’t really lost much weight, it doesn’t make much sense to continue treatment – there are alternative medications that may be more efficacious.  Another subset of phentermine users will be extremely unlucky in that they’ll experience adverse reactions or debilitating side effects.

Should you experience adverse reactions or debilitating side effects, it makes no sense to continue treatment – regardless of weight loss.  That said, most phentermine users will experience a blend of its therapeutic effect (weight loss) and side effects.  If the therapeutic effects are prominent and the side effects aren’t overly bothersome, it may be smart to continue treatment.

On the other hand, if therapeutic effects are only modest and side effects are of moderate or severe intensity, it may be better to cease phentermine usage.  For many individuals, tracking the severity of phentermine side effects in a journal can help them get a big picture understanding of tolerability over time.  If side effects documented in a journal reveal that the drug is well-tolerated at the beginning of treatment, but gradually worsen over time and impair quality of life – it may be time to consider stopping treatment.

Oppositely, if the journal entries suggest that side effects are gradually improving over time – it may be a good idea to continue treatment.  Journal entries can be easily reviewed and should help you keep track of side effects to report to your doctor.  Ultimately it will be up to you to decide whether the benefits of phentermine outweigh the side effects, and if so, whether you can tolerate the side effects that you experience.

Possible ways to reduce Phentermine side effects

If you’ve been taking phentermine and are experiencing side effects, there may be some useful strategies to employ for side effect mitigation.  Examples of some ways by which the number and/or severity of side effects can be reduced while taking phentermine include: ruling out contraindications, decreasing dosage, utilizing adjunct supplements, and modifying dosing parameters.  Prior to implementing any of the strategies listed below, be sure to verify safety and feasibility with a medical professional.

  1. Rule out contraindications: Though many individuals will end up taking phentermine for weight loss, not all will be cognizant of possible contraindications. There are numerous medical conditions in which phentermine usage is contraindicated (e.g. heart disease). Failure to rule out these contraindications before taking phentermine increases risk of serious adverse events and deleterious side effects.  Always consult a trained medical professional to evaluate your current health status and ensure that phentermine ingestion is safe.  You’ll also want the professional to analyze whether medications and/or supplements you’re using are safe to take with phentermine.  As was already noted, taking neuropsychiatric drugs such as MAOIs, even 2 weeks before taking phentermine – increases odds of a serious adverse event.
  2. Dosage reduction: If you’ve ruled out all possible medical and pharmacological contraindications with a doctor, the next best thing to do is analyze your dosage. Many individuals taking phentermine resort to using the highest possible dose (37.5 mg), or possibly even a supratherapeutic dose (e.g. above 37.5 mg). It is important to emphasize that the greater the dosage of phentermine you ingest, the more influence it has over endogenous homeostatic neurobiology – thereby increasing likelihood of side effects.  Your goal should be to take the minimal effective dose, or the lowest possible quantity of phentermine necessary to facilitate weight loss.  By avoiding the high doses, you may be able to reduce the severity and/or occurrence of troubling side effects.
  3. Slow titration speed: Some individuals may initiate high-dose phentermine treatment rapidly, titrating up to the highest dose in a period of a few days. Others may skip the titration process altogether and commence treatment with the 37.5 mg phentermine dose. Starting at the highest phentermine dose may shock a person’s central nervous system due to the fact that it wasn’t prepared for such a potent stimulus and/or alteration.  As a result, those who immediately start treatment with a high dose may be more likely to experience severe adjustment-related side effects.  However, the severity of these adjustment-related side effects may be averted if a person starts with the lowest dose and titrates it up over an extended duration (e.g. weeks).
  4. Co-administration: If your doctor has tried tinkering with your dosage, but side effects don’t improve, you may want to evaluate whether any adjunct agents may help you cope with side effects that you’re experiencing. For example, someone who experiences insomnia and sleep disturbances while taking phentermine may find that administration of an adjunctive hypnotic (sleep inducer) before bed attenuates the insomnia and improves sleep quality. Another person who experiences severe nausea may find it helpful to take an adjunct antiemetic agent.  Work with your doctor to pinpoint your most debilitating side effects and ask whether any co-administered drugs or supplements would be safe attenuators.
  5. Alter administration parameters: The parameters associated with phentermine administration may affect the side effects that you experience, as well as the side effects you perceive as most debilitating. Multiple administration parameters that are subject to manipulation include: time of administration, as well as ingestion in a fed (with food) or fasted (without food) state. If you’re experiencing insomnia every time you take phentermine in the afternoon at 1:00 PM, it may be worth testing whether insomnia improves if you shift time of administration to 5:00 AM.  Additionally, if you’re experiencing certain side effects from taking phentermine with food (e.g. stomach aches), you may want to test whether taking it in a fasted state (without food) decreases your stomach aches.  A person could also experiment with duration since food intake before and/or after administration, as well as the types of food ingested.  For example, a person may find that eating protein 2 hours before taking phentermine and no food for at least 3 hours after phentermine minimizes side effects, whereas another person may report the opposite.
  6. Strict adherence to schedule: Phentermine is recommended to be ingested at the same time each day, usually in the morning. If you fail to take phentermine at the same time each day, it’s possible that administration an hour or two later than the previous day may alter your circadian rhythm, which could result in more side effects. You may want to set a highly-specific time to administer phentermine and strictly adhere to this administration time to avoid throwing off your circadian rhythm.  Assuming your body can expect to receive phentermine regularly at the same time each day, some side effects may be fewer.  Plus, it is possible that if you’re constantly lackadaisical about administration time, you may go into brief periods of between-dose withdrawals – which may be unpleasant.
  7. Avoid unnecessary substances: Individuals that are taking phentermine with a host of other medications and dietary supplements, or are ingesting alcohol and/or illicit drugs during treatment – it is reasonable to speculate that side effects may be more severe. Even if the substances you’re using aren’t medically contraindicated, it is possible that they may be affecting the pharmacokinetics of phentermine and/or enhancing certain mechanisms of its action – leading to severe side effects. For this reason, unless a substance is medically necessary and safe to take with phentermine [as said by your doctor], you may want to eliminate all unnecessary agents from your regimen.  Elimination of unnecessary substances may reduce the severity of certain side effects (e.g. anxiety from drinking caffeine with phentermine).
  8. Continue using: If you’ve only been taking phentermine for several days, side effects may be severe due to the fact that your body hasn’t fully adjusted itself to the drug. Many side effects that are experienced during the first several weeks of treatment end up diminishing in intensity and/or abating altogether after a month or two of treatment. For this reason, sometimes the best strategy for side effect mitigation is to continue using phentermine in hopes that side effects will decrease as your body is given more time to adjust itself to the drug.

Note: It is possible that some individuals may try all of the aforementioned side effect mitigation strategies without any improvement in the number and/or severity of side effects.  In the event that you find it difficult to minimize side effects, you’ll want to work with a doctor to discontinue phentermine treatment.  Phentermine should only be discontinued under medical guidance due to the fact that withdrawal symptoms are often difficult to manage.

Have you experienced Phentermine side effects?

If you’ve taken phentermine and experienced side effects, be sure to discuss them in the comments section below.  In your comment, mention the specific side effects that you’ve found to be most debilitating or impairing.  To help others get a better understanding of your situation, provide additional details such as: the dosage of phentermine you take, whether you use other drugs and/or supplements along with phentermine, as well as the cumulative duration over which you’ve been taking phentermine.

In the event that you’ve been using phentermine for a long-term, have you noticed that side effects changed over time?  In other words, have you noticed that certain side effects that you experienced during the early stages of treatment subsided after several months and/or that new side effects emerged after many months of treatment?  Also document whether, in your experience, the therapeutic weight loss derived from phentermine has been more significant than the side effects – or vice-versa.

Among those that have managed to deal with side effects from phentermine, share any coping strategies or tactics that you’ve employed to make treatment more tolerable.  Realize that most phentermine users will have some side effects due to the psychostimulatory nature of the drug, but perceived tolerability will be subject to individual variation.  Ultimately it will be up to you to listen to your body and decide whether you can tolerate phentermine treatment.  Even if you struggle to tolerate phentermine, there are plenty of other weight loss drugs on the market.

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