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Finding the “Minimal Effective Dose” of Antidepressants & Other Drugs

When it comes to any psychotropic medication, many people simply take whatever dosage is assigned to them by their doctor. Unfortunately since most psychiatrists are bombarded with requests from patients that they want to feel better immediately, the demanding nature of the patient forces the psychiatrist to prescribe a relatively high dose. In some cases, a person may be thrown on a moderate to high dose of a psychiatric medication immediately in hopes that it will work quicker and be more effective than a lower dose.

While this strategy may be beneficial in the short term for certain patients, it isn’t always a great strategy. It may in fact produce quicker results and improvement in a person’s condition, but quicker is not always better. In many ways starting at a moderate to high dose of a specific drug could actually account for the drug not working properly or resulting in unwanted side effects. For this reason, patients and psychiatrists alike should be focused on finding the “minimal effective dose” on an individual basis.

Minimal Effective Dose: Subject to Individual Variation

The minimal effective dose of any drug is considered the minimum amount of a particular drug that it takes to obtain therapeutic effects. While most studies seek out to find the average “therapeutic” dose of a drug, scientists acknowledge that not everyone has the same reactions to these therapeutic doses. One person may experience no benefit at any dose, another may only find that they can tolerate a low dose, while another may require a high dose.

There are many individual factors that can influence the outcome of a particular treatment such as: genetics, stress, lifestyle, etc. Fortunately tests are being developed like GeneSight to determine specific individual genetic differences and determine how they will influence responses to psychotropic drugs. For example, a therapeutic dose for one person may be 60 mg of Prozac, yet for another, only 10 mg may prove to be highly therapeutic.

Since individual variation cannot be accurately determined, it is best to play it safe by gradually titrating upwards from the lowest possible dose on all psychotropic medications.

Dose-Response Curve (Effect/Side Effect Curve)

With all drugs there’s a well-established phenomenon called the “dose-response curve.” This curve is laid out in the form of a graph. On this graph, you could essentially plot out your reaction to an antidepressant drug by noting the dose and how you react to increases in dose. You would likely find that the lowest possible dose probably isn’t quite as effective as you’d hope for treating your depression.

However, you also find that as you increase the dose, the potential for side effects also increases. The goal is to find the “sweet spot” on the graph where a person is getting therapeutic benefit from the drug at the lowest possible dose. As the dose continues to increase, naturally the potential for side effects also increases because the drug will have a more potent influence over your physiology.

If you can’t find the side effect, you just don’t know what it is yet. The greater the effect of the drug, the greater the number of side effects. Disruption of physiological homeostasis. Body shuts down or alters endogenous production of certain things to compensate for the drug.

How to Find the Minimal Effective Dose

I have often stated that using the minimal effective dose is part of using antidepressants properly. Below I’ve outlined a step-by-step strategy that you can take if you’d like to ensure that you’re on the minimal effective dose of a particular drug.

1. Start as low as possible

Since most drug companies recommend starting at higher doses, it is recommended to always start as low as possible. In my personal experience, I’ve noticed that the “therapeutic doses” are often so powerful, that the side effects are overwhelming. To start as low as possible, you may need a pill cutter or to develop some sort of system. Be sure to talk to your psychiatrist about this when taking an antidepressant.

As an example, I’ll discuss Paxil – a drug that I have experience taking. Since the drug isn’t made in any dose less than 10 mg per pill, I cut the pill into 2.5 mg. I stay on the 2.5 mg for several weeks and assess whether it is working. If you are taking a pill with granules or beads, you may need to find a systematic way to measure the beads.

2. Gradual upward titration

If the 2.5 mg that I tried for several weeks isn’t working, I would gradually titrate upwards to the next highest dose of 5 mg. This would mean that I’d be taking half of a 10 mg Paxil pill as opposed to a quarter. If the 5 mg seems to be working, I would stay on that particular dose for as long as possible. If I notice nothing from the 5 mg, I would titrate upwards to the next highest dose of 7.5 mg or 3/4 of a pill. When titrating upwards, the goal is to be patient and titrate gradually as opposed to making large jumps in dosing.

3. Physiological adjustment phase

During each upward titration, there will be a period of time in which your physiology and neurochemistry will need to adjust to the elevated dosing. You may notice minor side effects and/or other changes in your functioning. This is simply a result of your body accommodating the influence of a foreign substance that you are now taking to treat a particular condition. Once you have adjusted, you should evaluate how well your current dose is working.

4. Efficacy evaluation

Each time you titrate upwards, it is important to reflect on the degree to which the drug is working. If it doesn’t seem to be working, it could be because the dose is too low. On the other hand, if you feel the drug giving you some benefit, but not enough, that’s a sign that you are just a titration or two away from finding an effective dose. In any event, it is important to evaluate your treatment at all levels of dosing – you may want to track this in writing. If you can afford it, I recommend using technology to improve psychiatric treatment outcomes.

5. Maintenance

Once you’ve found a dosage that seems to be helping treat your particular condition, it is relatively simple to maintain it. Since you’ll have gone through this process, you will be fully aware of what the minimal effective dose is for you as an individual. If you found a dose lower than the average therapeutic dose to be effective, you will get to enjoy the benefits of the medication and likely will experience less side effects and an easier withdrawal compared to those taking higher doses.

Why take the minimal effective dose? (Advantages)

There are many advantageous associated with finding the minimal effective dose of any psychotropic (or even non-psychotropic) drug. Taking the minimal effective dose allows you to get the therapeutic benefits, while ensuring that you will suffer less side effects than at a greater dose.

  • Adjustment: By titrating up to the minimal effective dose and starting with the lowest possible dose, you are giving your body a greater adjustment period. This will allow your physiology to naturally adapt to the drug rather than being shocked by a stimulus that is introduced at a high dose. A high dose stimulus could theoretically serve as a jolt to your nervous system, making for a shaky adjustment period.
  • Easier withdrawal: When you are taking the minimal effective dose, it ensures that your withdrawal will be easier than if you were taking a higher one. Those taking higher doses have created a more significant gap in functioning between homeostasis and drug-induced physiological change. At higher doses, the amount of drug-induced change is greater than that at lower doses. Therefore the gap to recover to homeostatic functioning is lesser at a minimal dose compared to an unnecessarily higher one.
  • Fewer side effects: Regardless of the dose of drug you are taking, there is always the possibility of side effects. However, you are significantly minimizing both the severity and number of side effects that will occur when you take less of a particular medication. Troubling antidepressant side effects like weight gain and sexual dysfunction are often less problematic at lower doses.
  • Less tolerance: Since tolerance occurs with every drug, it is important to make sure you are taking the smallest effective dosage. By taking the smallest dose, you will have less of a tolerance to a drug than a person tolerant to a higher dose. You will also have the option of gradually increasing your dose in the future should you develop tolerance. Furthermore, the lower your tolerance threshold, the easier it will be to withdraw should you want to pursue withdrawal.
  • Med-sensitive individuals: A significant number of people are highly sensitive to the effects of drugs – particularly psychotropics. This means that if they are given a standard therapeutic dosage of an antidepressant, it may shock their nervous system and be difficult for them to tolerate the drug’s effects. A standard dose for a highly med-sensitive individual may have the same effect as a high dose in your average person. For these individuals, there is a clear need to start with the lowest possible dose and gradually titrate upwards.
  • “Missing the boat”: Many people skip trying the lowest possible dose of a medication and I would argue that for certain people, that’s a mistake. While drugs have therapeutic guidelines for a reason, it doesn’t mean that they apply perfectly to everyone. Some people may actually find that low doses of a medication are the only ones that work. In other words, standard or high doses may not work, but low ones do. If you don’t actually try low doses, you’ll never know how whether they’ll provide benefit.
  • Physiological control: The greater the dose of the drug you are taking, the more control it has over your brain and physiology. When you double the dose or even increase it, you are giving it more influence over your nervous system. This often leads to further disruption of homeostatic processes and an increasing number of unwanted effects.
  • Superior efficacy: Always keep in mind that there is significant individual variation when it comes to determining therapeutic dosing. For one person, a therapeutic dose may be extremely low and for another it may be high. It should be noted that using a the minimal effective dose may actually prove to be of superior efficacy than using higher doses. This is because at higher doses, some of the therapeutic benefit may be overridden by side effects.

Disadvantages of finding the minimal effective dose…

While for most people (especially those new to psychiatric treatments), starting with the lowest possible dose is an optimal strategy, some people may have qualms with this approach. There are only a couple of drawbacks that are important to highlight. For some individuals with severe conditions, they need some sort of instant gratification and the titration method won’t be sufficient.

  • Lack of instant gratification: When a person jumps on a high dose of a drug, they tend to feel something pretty quickly. Those taking lower dose formulations may not really notice much of anything. It may take time to gradually titrate upwards and find an optimal dose. In the case of a person who is severely depressed, there is always a chance that throwing them on a high therapeutic dose will quickly lift their depression. This is largely due to the sheer potency of the drug and the immediate effect it elicits upon neurotransmitters and the nervous system.
  • Requires patience: Many people being treated with antidepressants do not have the patience to conduct gradual titrations upwards from the lowest possible dose. In many cases one may consider this to be risky in that a severely depressed person is unlikely to get any sort of benefit. While for many people the lower doses may not be effective, for some they will. Unfortunately it requires patience, which may not be practical for someone who is suicidal and in need of immediate relief.

Factors that may influence individualized minimal effective dose

There are several factors that are believed to influence the minimal effective dose. Things like how much you weigh, whether you take other medications, your degree of internal awareness, and whether you’ve used drugs in the past can all influence how you react to your current medication.

1. Body weight

It is believed that body weight plays a fairly significant role in determining someone’s reaction to a particular drug. In general, most doctors prescribe dosage based on age rather than weight. Most common sense would suggest that someone who is bigger can handle a greater amount of a certain drug than someone who is smaller. Therefore someone who is of smaller stature and body weight may find that a lower than average dose is highly effective, whereas someone who is considered large may not even feel the effects of a smaller dose.

2. Other drugs/medications

Do you currently take any other medications? Anyone who is taking a medication in addition to a new drug that they are trying may notice a couple of things. The first is that there could be an interaction between the two medications, leading to some sort of synergistic effect. This is common when a doctor prescribes a particular antidepressant augmentation strategy.

On the other hand, the other drug that a person has been taking may in some ways reduce the efficacy of any newly introduced medication. Therefore a person may need a higher therapeutic dose than they would’ve needed had their nervous system not been under the influence of the first drug. It should be noted that “other drugs” should not be limited to pharmaceuticals, this can also include illicit drugs, supplements, and caffeine.

3. Individual Physiology

On an individual basis, many factors come into play such as: stress level, genetic expression, physiology, hormone levels, nutritional deficiencies, exercise habits, sleep quantity, etc. There are so many individual factors that could have a significant influence on the outcome of your particular treatment.

In other words, someone who isn’t eating healthy or exercising may require a higher dose to feel a therapeutic effect of a particular drug. Others who are eating the best diet for depression and/or eating fish for antidepressant efficacy may notice that their medication drug works quicker. Those who are short on sleep, have high stress, and don’t exercise may require a higher dose of the drug to experience therapeutic effects.

4. Internal awareness

There are people that have more of an internal awareness that will quickly notice any changes in functioning as a result of a medication. While they may not have as extreme of a reaction as those who are hypersensitive, they do have a clear understanding of what the drug is doing to them and whether they are experiencing side effects.

On the other hand, there are individuals who are more focused on external events and people. These individuals may not pick up on what the drug is doing to them and may be less quick to notice how they react to a particular medication. Those who are internally-oriented may have less tolerability for higher doses.

5. Hypersensitivity

Some individuals taking antidepressants are hypersensitive to any medication. In other words, they are acutely aware of any side effects and even minimal changes in physiological functioning. These tend to be high-strung individuals that carry a high degree of anxiety. The hypersensitivity generally means that a lower dose must be used if there is any hope that they will be able to tolerate the treatment.

6. Past drug/medication usage

Whether you’ve used antidepressants or other drugs in the past will influence any reaction to the current medication you’re trying. If you’ve never used any antidepressants or psychotropics before, your homeostatic processes are still in tact. Those that have used antidepressants before their current medication may have a lingering chemical imbalance or some sort of tolerance to the effects of drugs within the same class (e.g. SSRIs).

  • Chemical imbalance: Anytime you’ve taken an antidepressant before, there’s a possibility that the medication actually caused a chemical imbalance that wasn’t previously there. If you were taking an SSRI for example, you may now have altered serotonergic functioning. If you do not properly taper off of the drug and simply leap to another antidepressant, you will be engaging in what I like to call “antidepressant roulette.” This further disrupts natural neurotransmission within the brain and leads to poorer efficacy of any future antidepressant that is tried – especially if they are from within the same class.
  • Tolerance: Developing a tolerance is highly common among those taking antidepressants. If you’ve ever noticed an antidepressant stop working, you have experienced this directly. When you build tolerance to a drug, it decreases the likelihood that lower doses of other medications (particularly of the same class) are going to be effective. Therefore you may now end up only responding to abnormally high doses.

Note: Many of these factors also apply to whether a person notices an antidepressant works immediately vs. takes a long time to work.  Those who notice that a drug works immediately probably have never been on a medication before and may be at lower body weights, while those who notice a drug takes a long time to work may be at greater body weight and/or have been on antidepressants before.

Have you tried the minimal effective dose approach?

If you have already tried taking the minimal effective dose of an antidepressant or other drug, feel free to share your experience in the comments section below. For some people the recommended “therapeutic” range is too high, yet for others it may be perfect. Yet for others the recommended therapeutic range may not be high enough. As was mentioned, there are clear advantages associated with taking a minimal effective dose approach, but not everyone has the patience to pursue this strategy of taking medications.

Note: Although this article was targeted to antidepressants, the concepts and theories apply to other drugs as well such as: antipsychotics, eugeroics, supplements, and illicit drugs.

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{ 8 comments… add one }
  • Liz January 30, 2016, 5:19 am

    I found this to be very refreshing to read and inspirational hope for people who feel like they’ll never be able to maintain the positive effects of some psychotropic medications like antidepressants.

  • Sara O'connor May 13, 2016, 11:38 am

    Helpful article, will try medication at lowest dose possible and hopefully work up.

  • Peter May 24, 2016, 12:52 pm

    I think the author has failed to establish a strong argument for the approach they are recommending. Arguing for caution by its very nature sounds reasonable, but caution can be motivated by emotions. The author talks about “average therapeutic dosages” as if the are arcane numbers, but its really the “minimum therapeutic dosage” that is arcane. The point I’m trying to make is that when the average therapeutic dosage is known, then beginning treatment at a dosage level that is magnitudes lower (i.e. 2.5mg) is daft.

    Our knowledge may limited, but it’s not so limited that a person suffering depression has to languish for months on dosages that are predicted by established research to be ineffective, on the off chance that they may be one of the very few people who are hypersensitive. You have to play the odds. Time can be critical in treating depression. It’s not much use if the patient suicides while the doctors busy trying to figure how best to cut a pill into 12 slices.

    Of course the ultimate goal is to find the minimum therapeutic dosage, but caution for cautions sake is not the answer. What should be done instead is to follow dosage guidelines based on existing data, and average therapeutic dosages are the single most important piece of data we have, as imperfect as they may be. I also disagree with the authors comment that doctors are being pressured into proscribing higher dosages.

    On a pure anecdotal level as speaking solely from personal experience I have witnessed and heard reports of doctors influenced by the growing backlash against medication, but still fearing inaction, instead prescribing dosages well below therapeutic amounts as if in compromise. I believe that this is an emerging trend and that over prescription of anti depressants in laughably low dosages will be the next big issue.

    Debate about effective treatment for depression is becoming dangerously polarised.

  • bill w June 22, 2016, 5:07 pm

    Too bad the author doesn’t have some statistics on the numbers of patients who give up and commit suicide while waiting for the dosage to reach the therapeutic range! We say depression is dangerous but commonly the psychiatric community seems disconnected. What is needed is statistical info from phamacists on what dosages are actually used. I am sure any big mail order pharmacy has reams of such data.

  • Be be B July 2, 2016, 8:49 pm

    Being a hypersensitive medication responder I am happy to see that there is conversation regarding this topic. I have historically had conflict with my doctors in terms of medication non-compliance because I cannot tolerate the high doses that they want me to take yet I do need medication.

    So if I try a new medication I do need to begin at a lower than typical starting dose, otherwise I am most likely going to stop the medication because of intolerable side effects. An example would be Lyrica. The first doctor started me at 75 mg. When I called to tell them that it was impossible for me to continue and asked if I could start at 25 mg (as read online) I was told no it was a trial and to just stop taking it.

    Later a second doctor allowed me to take it at a 25 mg dose three times a day. I began at 25 mg had excellent results and never increased. However I was noncompliant since I did not take it three times a day. However I can also understand that until it has been established that someone is hypersensitive to medications that normal medication recommendations would be followed.

  • Eugene August 15, 2016, 2:47 am

    In my 18 years experience, I have found that when I take a new prescription, starting at the “therapeutic” level always produces an effect within a day. The effect may be good or it may be bad. The bad is the side effects. I haven’t found any good effect for me when starting at “therapeutic” dose. Side effects (for me) can be very intense and this can make a person wish to die, as in commit suicide.

    So, I don’t agree with this start everyone at this arbitrary level based on a rounded average. Therefore, I have come to this conclusion for myself. I let the doctor prescribe it and I regulate it. I know my body. The doctor “PRACTICES” medicine and filters my words through their point of view. How many of them have taken a therapeutic dose just once to see how it feels?

    Don’t tell me they shouldn’t take it, even once, since they don’t need it. That is what they do to us! I have had so many meds PRACTICED, ahem… prescribed to me that I didn’t need, and guess what? I didn’t continue to take them! It doesn’t take days or weeks of added suffering to know if a med is helping or hurting.

    Every person has the right to adjust their meds. I am NOT advocating abusing medicine for a high. What I am saying is pay attention to what your body is telling you and read the information supplied with the scrip. It will tell you what to expect. Remember knowledge is power and there is so much legitimate info on line now,so anyone can read and better equip their self to be more informed and confident when visiting their doctor.

    Doctors go through years of education and I do not think myself equal to them in their field, but I do have the advantage of focusing on a few meds and not the entire field of pharmaceuticals. I hope this rant helps someone to actively manage their meds and not be passive or intimidated when dealing with their Healthcare Professional.

    Tom Petty says it plain and simple. “You don’t know how it feels to be me”. Too many doctors. Too many pills. Peace, and may the pharm be with you.

  • Tim Smith October 15, 2016, 9:03 am

    I was badly depressed in 2013 for the first time ever and after Mirt and Cit I found Prozac 20mg helped even me out. I was so ill I probably didn’t even notice any side effects so I stayed on it for about a year just managing to function OK. I weaned off very slowly and looking back as I reduced by 10% every 2 weeks I did feel much better. Once weaned off fully and the drug out of my system some months later I started to feel bad again so went back on at 20mg.

    After 2 weeks I had just about every side-effect going and headache so bad I had to stop for a few days. I have gone back on at 5mg as when I look back over how I felt at particular doses I am sure I felt great on a low dose. So far on this reduced amount I have minimal side effects and my mood is stable and I feel pretty good. I think it’s all down to individual make-up so if you cant tolerate the “standard” dose it’s definitely worth trying low.

  • Aurora December 3, 2016, 9:08 am

    I have a history of anxiety/depression and also reactions to antidepressants. I have learned through experience that I cannot tolerate starting on low doses, let alone normal doses of SSRI’s, so I have been prescribed Mirtazapine. My doctor told me to take 15 mgs at night, but I knew that would be way too much for me.

    I used a pill cutter and took approximately 2.5 mgs at midday on the first day instead of before bed as I wanted to feel how it was affecting me. Thirty minutes after the first 2.5 mg dose I could feel the effect. I felt very sedated, almost like jet lag really, but really calm and that continued through the evening.

    I had my first full nights sleep in months. I have taken the 2.5 mg dose for 4 days now and will start to increase in a couple of days. The effect it has had on my insomnia is great! I feel waves of tiredness during day as well, but that’s ok. No anxiety with this med or gastrointestinal issues and I’m hoping as I increase it will also help mood. I intend to find the lowest possible therapeutic dose for me.

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