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Saphris (Asenapine) & Weight Gain: What Should You Expect?

Saphris (Asenapine) is an atypical antipsychotic medication that was approved in 2009 for the treatment of schizophrenia and bipolar disorder.  It is a relatively new atypical antipsychotic, and is considered a chemical derivative of the tetracyclic antidepressant (TeCA) mianserin.  It is manufactured in a sublingual format, which some may perceive as an upgraded or novel modality of administration.

Due to the fact that the drug is relatively new and many people fail to achieve symptomatic relief from older medications, many people have turned to Saphris.  Although evidence suggests that it may not be as effective as other antipsychotics for schizophrenia, certain individuals find it highly effective.  Perhaps most alarming was that there were significant rates of discontinuation of the medication in clinical trials.

High discontinuation rates during clinical trials are generally a sign of intolerable, adverse reactions.  One of many common adverse reactions associated with Saphris is weight gain.  While most medical professionals consider the weight gain to be moderate, gaining a significant amount of weight on Saphris may contribute to depressive symptoms stemming from poor self-image and may create an entirely new set of health risks associated with obesity.

Saphris (Asenapine) and Weight Changes (Scientific Research)

There is significant scientific research suggesting that Saphris is unlikely to cause significant weight gain, regardless of the term of administration.  While users gained slightly more weight in long-term trials (12+ weeks), the weight gain was not significantly different from individuals involved in short-term trials (less than 12 weeks).  The average reported weight gain from Saphris was under 3 lbs. after an entire year’s worth of treatment at 5 mg or 10 mg dosages.

2014: Researchers compiled a report documenting weight changes and metabolic effects derived from Saphris and Zyprexa compared to placebos in adults.  Data was extracted from 17 trials comparing Saphris to a placebo at dosages of 5 mg to 10 mg (taken twice per day).  The number of participants was 1,748 and the medication was ingested for a period of up to 6 weeks.

Baseline bodyweight, BMI, fasting lipids, and glucose levels were assessed.  It was reported that weight changes from Saphris were more significant than a placebo and similar regardless of psychiatric diagnosis.  Changes in fasting glucose were considered significantly elevated among Saphris users compared to those taking a placebo.

That said, when Saphris was compared to Zyprexa, it appeared to produce less substantial weight change and superior levels of various biomarkers (e.g. cholesterol, glucose, LDL, triglycerides).  While each respective drugs’ efficacy is subject to individual variation, it appears as though Saphris is less likely to significantly disrupt various homeostatic biological processes compared to Zyprexa.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24499969

2013: A study published in 2013 documented various adverse effects that occurred in at least 2% of Saphris users.  One of these adverse effects happened to be an increase in bodyweight, occurring in approximately 3.5% of users compared to just 0.4% of individuals assigned to a placebo.  Other adverse effects that may have contributed to weight gain were sedation (occurring in 9.1% of users) and somnolence (occurring in 8.4% of users).

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539266/

2012: A publication from 2012 reviewed the literature of new atypical antipsychotics and determined that of Saphris, Fanapt, Latuda, and Invega – Saphris was most associated with significant weight gain.  Not only was weight increase more likely to be statistically significant based on a review of 5 trials (with 1,360 participants), the average weight increase was more substantial.

Based on 3 placebo-controlled, short-term trials (spanning less than 12 weeks), average weight gain associated with those taking Saphris was an estimated 2.55 lbs.  Longer-term, placebo-controlled trials suggested that average weight gain on Saphris was just under 3 lbs.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22900950

2011: A report from 2011 documented side effects associated with Saphris for the treatment of bipolar disorder.  It was documented that an estimated 31% of participants reported significant weight gain.  This figure differs from the estimates promoted to the general public by the manufacturers of Saphris; they suggest that only 6% of users gain weight.

The 31% of individuals experiencing weight gain is thought to be an improvement over an estimated 55% of users who report weight gain on the medication Zyprexa.  The mechanisms associated with weight gain from Saphris may be related to alterations in fasting blood glucose levels that have been noted in approximately 18% of users.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140314/

2011: Another publication from 2011 documents the likelihood of gaining weight on Saphris.  Based on placebo-controlled trials, the likelihood of individuals experiencing significant weight gain (at least 7% of bodyweight increase) occurred in an estimated 5% of users.  Authors noted that no significant metabolic alterations were recorded as a result of Saphris.

They did note that Saphris had increased propensity to cause somnolence in an estimated 24% of users.  That said, it is important to note that the reported weight gain experienced in less than 5% of users was based off of data from 3-week trials.  Longer-term trials of the medication may have resulted in more substantial weight change.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20950326

2011: A study published in 2011 reported the side effects associated with Saphris for the treatment of schizophrenia.  It was administered sublingually in 5 mg or 10 mg dosages and was considered well-tolerated by participants.  Researchers suggested that Saphris didn’t significantly affect lipids and glucose levels.

They did note that it promoted sedation, but was associated with a relatively low likelihood of weight gain.  This report documented average weight gain of less than 2.2 lbs. after a full year’s treatment.  Perhaps some of the weight gain experienced from Saphris is based on its sedating properties.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22217438

2011: Another report from 2011 documented that some weight gain is observed among those taking Saphris compared to a placebo.  However, the weight gain is generally less significant when compared to other atypical antipsychotic medications such as Risperdal and Zyprexa.  Authors highlighted the fact that in a clinical trial spanning over 6 weeks, only 4.3% of Saphris users experienced significant weight gain.

It was suggested that Saphris may be less likely to cause weight gain as a result of its mechanism of action.  Specifically, compared to other antipsychotics, Saphris doesn’t elicit significant effects on the M3 muscarinic receptor as an antagonist.  It has long been suggested that various antipsychotics like Zyprexa have a high affinity for the M3 muscarinic receptors which ultimately contribute to significant weight gain.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924192/

2011: Researchers document that no more than 5% of those taking Saphris experience clinically relevant weight gain.  In addition, they report that no substantial changes in baseline lipids, glucose, or liver enzymes are apparent among individuals taking Saphris at 5 mg and 10 mg (trice daily) compared to a placebo.  According to this report, your chances of gaining weight as a result of Saphris are relatively slim.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21655346

2010: In a double-blind trial of Saphris for those with schizophrenia, it was determined that dosages of 5 mg or 10 mg daily resulted in modest weight gain.  The study incorporated a large sample of 913 participants.  That said, weight gain after a full year of treatment was under 2 lbs. – substantially less than Zyprexa.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20205074

2009: A Phase III randomized, double-blind clinical trial assessed Saphris for the treatment of schizophrenia in 1,219 participants.  Significant weight gain was reported in just under 15% of those taking Saphris compared to 36% of those taking Zyprexa.  Results from this clinical trial indicate that Saphris is less than half as likely to cause clinically significant weight gain among users compared to Zyprexa.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19851515

Consensus: Saphris causes modest weight gain; nearly weight neutral

It appears as though Saphris may cause a small amount of clinically significant weight gain (at least 7% of your bodyweight) in between 5% and 7% of users.  Therefore many doctors and psychiatrists may consider this atypical antipsychotic to be relatively “weight neutral” compared to others.  When compared to older atypical antipsychotics like Zyprexa and Risperdal, the likelihood of weight gain is miniscule.

Assuming you end up gaining weight from Saphris, the literature indicates that average weight gain after 1 year is under 3 lbs.  Between 5 and 7 people out of 100 will gain more than 7% of their bodyweight on the drug.  For most people, gaining a little bit of weight from Saphris won’t be a big deal assuming it is successfully managing symptoms of schizophrenia or bipolar disorder.

How Saphris Causes Weight Gain

It is important to acknowledge the fact that weight gain associated with Saphris may be underreported in the literature.  Many studies are relatively short-term (several weeks) and even the long-term trials do not mimic outcomes among those who have taken the drug for much longer than a full year (e.g. 5 years).  Weight gain from Saphris may be due to a unique combination of the factors listed below.

  • Appetite increase: It is well known that many antipsychotic medications stimulate appetite. If you start taking Saphris and notice that your stomach is constantly growling and you have suddenly developed an insatiable appetite, it may contribute to your weight gain.  Keep in mind that appetite changes may be temporary as your body adjusts to the medication.  However, assuming your appetite skyrockets and you find yourself raiding the fridge – it’ll be tough to keep the weight off.
  • Blood sugar increase: Some studies have demonstrated that Saphris spikes fasting blood glucose levels in an estimated 18% of users. Assuming your fasting blood sugar levels increase as a result of the medication, you may have a tougher time avoiding weight gain.  High levels of blood sugar result in increased stores of body-fat and elicit a cascade of other physiological changes that promote weight gain.
  • Fatigue: Certain users of Saphris will notice that their energy levels plummet and they feel lethargic. Individuals that experience lethargy as a result of the medication may end up spending more time on the couch, sedentary, or sleeping in bed.  As a result of lethargy-induced sedentarism, less calories will be burned and metabolism slows; the perfect storm for weight gain.
  • Fat storage: In many cases, users of antipsychotics like Saphris will notice that they begin building excess body fat. An increase in body fat may be caused by a variety of factors including metabolism slowing, hormone alterations, blood glucose concentrations, etc.  Saphris is thought to alter an array of physiological functions, which may lead to accumulation of fat stores.
  • Food cravings: In addition to an appetite increase, some people may notice that they develop significant cravings for sweets (sugary foods) and carbohydrates. When consumed in excess, sweets and carbohydrates further spike blood glucose levels and contribute to weight gain.  Should you notice that you’re craving candies, potato chips, and fast-food – it could be related to the medication.
  • Hormone levels: There is preliminary evidence that long-term administration of antipsychotics can lead to spikes in the hormone ghrelin. Heightened levels of ghrelin are associated with increased hunger.  In other words, consistent administration of Saphris may be increasing your ghrelin, which causes you to feel hungry all the time.  When you feel hungrier, you’ll have a difficult time resisting food and will gain weight.  It is important to consider that an array of other hormones may be affected by Saphris such as testosterone, estrogen, cortisol, etc.
  • Metabolism slowing: It is common for your metabolism to slow while taking Saphris. The slowed metabolism may be due to increased sedation, hormonal changes, and less physical activity.  While you may make a concerted effort to counteract this metabolism slowing my hitting the gym harder and selecting healthier foods, it may not prove effective for everyone.
  • Motivational deficit: It is possible to experience a decrease in motivation to hit the gym or make healthy choices as a result of Saphris. Since the drug is substantially altering your neurochemistry, the drug-induced changes may alleviate your symptoms of schizophrenia (or bipolar disorder), but may simultaneous sap you of energy and motivation.  A reduction in motivation can indirectly cause weight gain.
  • Sedation: Saphris is known to cause significant sedation and somnolence among users. In fact, the sedation and somnolence are much more likely to occur than weight gain.  However, it is important to consider that a consequence of sedation from Saphris could be increased weight gain.  If you feel sedated, you may sleep excessively and avoid exercising – which will likely promote weight gain.
  • Social eating: Assuming Saphris is successfully managing symptoms of your psychiatric condition, you may feel happier and more inclined to socialize. Increased socialization is often associated with going out to eat.  The cultural revolution of the past hundred years resulted in an increased number of unhealthy fast-food restaurants and choices.  If you’re going out to eat more since taking Saphris, the foods you’re eating may be causing the weight gain.
  • Taste improvement: Saphris is known to significantly alter neurochemistry, which helps alleviate symptoms of psychiatric illnesses. Some of the alterations to neurotransmitters may result in perceived taste enhancement.  Those that experience enhanced taste as a result of taking Saphris may be more drawn to food, particularly unhealthy foods like simple carbs and other sugar-laden sweets.

Note: It is important to consider that weight gain on Saphris may be caused by a variety of the aforementioned factors.  In other words, someone may gain weight as a result of sleepiness, metabolic slowing, motivational deficits, junk food cravings, and blood sugar increases.  Other individuals may gain weight mostly due to just one or two factors.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21474903

Factors that influence weight gain on Saphris (Asenapine)

It is important to consider the fact that weight gain on any medication is due to an array of individual factors.  Two people may take Saphris, yet one may experience major weight gain in a short period of time, while another may experience no significant weight gain.  Factors that may influence weight gain include: medication interactions, lifestyle, genetics, duration of treatment, and dosage.

1. Interactions

It is important to consider the possibility that Saphris may be interacting with other medications to cause weight gain.  Furthermore, if you start another medication at the same time as Saphris, you may want to investigate whether the weight gain may be more related to that particular drug.  In many cases, people gain weight as a result of synergistic mechanisms of psychiatric medications.

For example, someone taking Saphris along with an antidepressant may experience amplified food cravings, neurotransmitter alterations, hormone alterations, and metabolic slowing.  The combined effect of multiple (or a cocktail) of psychiatric drugs may be more likely to induce weight gain.  Similarly, certain medications that have a stimulatory effect may help offset any weight gain that may occur as a result of Saphris.

2. Lifestyle

It is important to consider an array of lifestyle choices that may contribute to weight gain including: dietary choices, circadian rhythm management, sleep hours per night, stress level, and daily physical activity.  Someone who normally eats an unhealthy diet, fails to get enough sleep, and is physically inactive may be more likely to gain weight on Saphris.

Someone who engages in an unhealthy lifestyle may have a difficult time distinguishing whether the Saphris caused the weight gain or whether increases in weight were caused by lifestyle choices.  It is also important to consider the fact that Saphris could exacerbate the effects of certain lifestyle choices such as sedentarism and/or eating unhealthy.  Exacerbation of poor lifestyle choices may result in more substantial weight increases.

3. Genetics

Many people make healthy lifestyle choices and don’t take any other medications along with Saphris that could promote weight gain, but still end up gaining weight.  This could be due to both neurophysiology and genetics.  People with certain genetic polymorphisms are thought to be at increased risk for obesity and weight gain.

Assuming you have unfavorable genetics for weight management, gaining weight on Saphris may be more likely.  In addition, some people have genes that don’t respond well to administration of Saphris.  You may want to consider using a test like GeneSight to investigate any potential interactions between Saphris and your genetics.

4. Dosage

In general, the greater the dosage you’re taking, the more likely you are to gain weight.  Specifically, the propensity of weight gain on Saphris may be a result of the dosage in relationship to your baseline bodyweight and/or size.  A larger person may require a greater dosage of the drug compared to a smaller person, but if the smaller person is administered the same dosage – weight gain may be more likely.

Increased dosages tend to provoke more weight gain due to the fact that more of the drug has influence over neurophysiological function.  Therefore if you want to minimize the likelihood that you’ll gain weight on Saphris, you should strive to take the minimal effective dose.  By taking the minimal amount of Saphris necessary for symptomatic relief, you minimize the drug’s influence over your body  and likelihood of side effects, including weight gain.

5. Time Span

It appears as though the longer you’ve been taking Saphris, the more weight you’ll end up gaining.  In part this may be due to establishing a tolerance to a particular dosage after an extended term.  Despite the fact that weight gain wasn’t significant for most over the course of a full year’s treatment, many people have taken Saphris for much longer than a year.

Those that have been taking Saphris for several years may end up gaining weight as a result of long-term neurophysiological changes made by the drug.  In addition, the longer term of administration may have resulted in dosage increases, which make weight gain more likely.  Short-term users of Saphris are less likely to gain significant weight compared to those taking it over a longer term.

How much weight will you gain on Saphris?

It is difficult to determine how much weight you’ll gain while taking Saphris.  Much of the weight gain you experience will be based on the aforementioned factors such as: medication interactions, lifestyle choices, genetics, duration over which you’ve taken the drug, and your dosage.  Someone who has been taking a high dose of Saphris and has certain genetic polymorphisms that predispose them to weight gain may pack on more significant weight than other individuals.

Short-term: Those that take Saphris over a term of less than 12 weeks tend to gain just under 2 lbs. within the first 3 weeks of treatment.  The literature suggests that you are unlikely to gain any significant weight if you use Saphris on a short-term basis.

Long-term: The FDA packaging insert for Saphris suggests that substantial weight gain is unlikely over long-term.  This is likely due to the fact that it is less likely to alter metabolic processes than other antipsychotics.  After a year’s worth of treatment, weight gain was reported as being under 3 lbs. on average.  It is unknown as to whether more substantial weight gain is experienced after several years of treatment.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21318056

Does everyone gain weight on Saphris?

Certainly not everyone will report significant weight gain on Saphris.  The exact percentage of people who experience clinically significant weight gain from Saphris isn’t well established.  However, most large-scale trials and reviews suggest that between 5% and 7% of all users will end up gaining significant weight.

The manufacturers of Saphris suggest that clinically relevant weight gain occurs in an estimated 6 out of 100 users.  Clinically relevant weight gain is defined as an increase of at least 7% baseline bodyweight following administration of Saphris.  In other words, if you weighed 200 lbs, you’d end up gaining a minimum of 14 lbs.

Despite the fact that most studies suggest weight gain occurring in an estimated 6% of users, other studies suggest more substantial figures.  For example, one study discovered that 19% of patients treated with Saphris experienced weight gain; this is over double the percentage reported in other studies.  Some have theorized that weight gain on Saphris may be related to a low baseline BMI and bodyweight before taking it, whereas those with higher BMIs may be less susceptible to weight increases.

Does Saphris’ therapeutic benefit outweigh the weight gain?

If you are taking Saphris, it is important to conduct a cost-benefit analysis to determine whether the therapeutic efficacy trumps the weight gain (and other side effects).  It is important to work with your doctor to assess degree of symptomatic improvement that you’ve derived from Saphris and compare the improvement to the unwanted side effects.  If Saphris is working brilliantly and has your symptoms of schizophrenia (or bipolar disorder) under control, you may not care about weight gain.

However, if you’ve packed on some serious poundage as a result of the medication, and it’s not working very well to manage your symptoms, it may be time to consider other options.  Understand that excess weight gain can contribute to a cascade of other general health problems such as diabetes and cardiovascular problems.  If you’ve gained a moderate amount of weight, and the drug is working fairly well, it may be tougher to determine whether continued treatment is warranted.

If you’re having a tough time determining whether to continue treatment and/or switch medications – talk to a medical professional.  They will help you track your weight, various physiological biomarker changes, and assess how well the drug is working.  Most research suggests that people are less likely to have a problem with weight gain compared to its degree of efficacy; many people have poor responses.

Have you gained weight from Saphris?

If you’ve taken Saphris, feel free to mention any weight changes you’ve experienced in the comments section below.  Report how much weight you gained, the dosage of Saphris you were (or are currently) taking, and the duration over which you’ve been taking it.  Can you be sure that the weight gain you experienced was from Saphris – or have you started other medications along with it?

Understand that it’s difficult for many people to accurately determine whether they gained weight from a medication and/or as a result of other lifestyle changes.  By maintaining the same: level of physical activity, sleep, stress, and diet – it is easier to chalk weight fluctuations up to Saphris.  For most people, Saphris will not be associated with nearly as significant weight gain as other atypical antipsychotics.

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