Do Antidepressants Work? The Effect of Publication Bias

A recent meta-analysis of the most commonly prescribed antidepressant drugs raises some very important questions for science-based medicine. The study: Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration, was conducted by Irving Kirsch and colleagues, who reviewed clinical trials of six antidepressants (fluoxetine, venlafaxine, nefazodone, paroxetine, sertraline, and citalopram). They looked at all studies submitted to the FDA prior to approval, whether published or unpublished. They found:

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

The press has largely reported this study as showing that “antidepressants don’t work” but the full story is more complex. This analysis certainly has important implications for how we should view the body of evidence for these antidepressants. It also illuminates the possible role of publication bias in the body of scientific literature – something that has far ranging implications for science-based medicine.

The Strengths and Weaknesses of this study

The primary strength of this analysis is that it looked at all clinical trials for these antidepressants submitted to the FDA prior to approval – whether or not the studies were published. The authors did this specifically to eliminate the effect of publication bias on the data. In pooling the data together using meta-analysis statistical methods the study also able to have much more power than a single study (the analysis included 5,133 total subjects). The study design also allowed for comparison of antidepressant efficacy for differing initial severity of depression – an important question for determining who should and should not be treated with antidepressants.

The study has numerous weaknesses, however. Because the study only looked at pre-approval clinical trials it did not account for all available data. Also, once a drug is approved study designs are more variable as they are no longer specifically designed to meet the criteria for FDA approval and may be more relevant to clinical practice. The analysis only considered a single measure of depression (Hamilton Rating Scale of Depression – HAM-D), and it is possible that other measures of depression may have yielded a different result. The study also included data mainly for severe depression, with only one study of moderate depression and now studies of mild depression. Finally it should be noted that meta-analyses in general are not highly predictive of the outcomes of later large definitive trials. The process of performing a meta-analysis itself has the potential to introduce bias and error.

What does this study mean?

This, of course, if the ultimate question for clinicians and the public – how should the results of this meta-analysis be incorporated into the current practice of medicine? This is a complex question, and can only be answered in the context of all available evidence on the use of antidepressants in the treatment of depression. Not all studies and not all systematic reviews and meta-analyses of the use of antidepressants in depression give us the same results. For example, this recent review found:

Paroxetine yielded consistently and significantly better remission (rate difference [RD]: 10% [95% CI = 6 to 14]), clinical response (RD: 17% [95% CI = 7 to 27]), and symptom reduction (effect size: 0.2 [95% CI = 0.1 to 0.3]) than placebo.

This review looked at multiple outcome measures, and pre and post approval trials, but only considered published studies. Therefore it had different strengths and weaknesses than the current review, and further study is needed to determine how best to interpret these conflicting results.

At this time it is premature to conclude that modern antidepressant medications do not work. There is sufficient evidence for efficacy to continue to use medication as part of the overall treatment approach to depression. The current consensus is that therapy is also a critical component of the long term treatment of depression, and therefore looking at the use of medications in isolation may not reflect their actual clinical use. Multiple studies have now shown that combination treatment (medications and therapy) are better than either alone. There is also evidence that medication treatment is more successful when multiple agents are tried in order to find the optimal treatment. These so-called “real world” treatments are not well reflected in the pre-approval trials considered in this analysis.

But this analysis does indicate that perhaps clinicians should consider alternatives to medication for patients with mild to moderate depression, and reserve medication for more severe patients or those who do not respond to non-medication modalities alone. It also emphasizes (together with other evidence) the need for combination therapy in many patients.

It is also important to note that depression is only one of many clinical uses for antidepressant medications. Other uses include anxiety, panic disorder, neuropathic pain, and eating disorders. Each indication should be considered on its own merits.

The role of publication bias

This meta-analysis is important for what it tells us about the role of publication bias, a term that refers to the tendency for researchers to be more likely to submit, and editors to publish, papers with positive results than with negative results. Therefore any review of the published literature is not a reflection of all evidence, but of a subset of the evidence biased toward positive outcomes. With regard to clinical trials of antidepressants, the pharmaceutical company sponsors of those studies had to report them to the FDA (and therefore they were accessible for this review) but they tended to publish only the positive studies. This is also not the only review to find such a bias. As my colleague, Kimball Atwood, has previously discussedTurner et. al. looked at trials submitted to the FDA for 12 antidepressants and found:

According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive.

We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.

This effect is also not limited to clinical trials of antidepressants, or even to pharmaceutical trials, but plagues all published medical research. Publication bias distorts the body of evidence upon which science-based medicine is dependent. It is a particular problem for systematic reviews and meta-analysis. It even has the potential for creating the impression that a clinical effect exists where it does not.

One way to compensate for the effect of publication bias is to rely more on large, definitive, high profile clinical trials. Such trials are usually the result of a consensus that emerges from a body of literature, with both proponents and skeptics agreeing on the study design, taking into account the results of previous weaker studies. Such trials tend to high profile, meaning that the results cannot be hidden away once the study is concluded. Large individual trials are therefore not subject to publication bias.

But we need to develop further strategies to minimize the effect of publication bias on the literature. One strategy would be to require that all trials involving human subjects be registered in a central database. The results of all human trials could therefore be accessible to researchers, whether or not the results were ever published. Such a system already exists for FDA drug trials, but should be expanded to include all human trials. Also, researchers should be encouraged to submit studies for publication, even when they are negative. And journal editors should make efforts to publish negative results, and not favor positive results that are more likely to grab headlines.

Posted in: Clinical Trials, Neuroscience/Mental Health, Pharmaceuticals, Science and Medicine

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21 thoughts on “Do Antidepressants Work? The Effect of Publication Bias

  1. Skeletor says:

    A couple of points on this

    1- The authors of this study included studies under 6 weeks in duration which is simply not long enough when evaluation these types medications.

    More criticisms by people much more qualified by myself can be found in the comments section for this article.

    2- I’m going to commit the “poisoning the well fallacy” here but by looking at the homepage of the lead author raises some questions about his motivation.

    It does seem suspicious when an author with an interest in CAM and who has previously published studies against anti-depressants in the past (also one in favor of St. John’s Wort) comes out with a study such as this one.

  2. Aaron S. says:

    Good post. It is easy to take these meta-analysis studies to extreme conclusions (like “it doesn’t work”), which I think is unfortunate for the Media to do. Though it’s not surprising.

  3. Fifi says:

    I second the “good post” and I appreciate the analysis. At the very least the meta-analysis has hopefully opened up a discussion which has been sorely needed for quite a long time now. It won’t necessarily help those in the US who are being given prescriptions because their health insurance doesn’t cover longer treatments like talk therapy or combined drug/talk therapy – that’s a systemic issue that has to do with profit margins – but at least it’s raised some important questions in a way that requires that they finally be addressed.

  4. Aaron S. says:

    @Fifi: By the way, I switched insurance so that I could see a psychiatrist soon about cognitive issues. My old insurance did not cover outpatient mental health at all.

  5. Dacks says:

    Dr. Novella,
    I’m glad you addressed this study, but I’m not sure whether this article sheds any light on the medicate/don’t medicate issue. You write that doctors should perhaps

    “…reserve medication for more severe patients or those who do not respond to non-medication modalities alone.”

    Speaking as a layman, I can’t see how withholding medication serves anyone’s interests. If the depression is severe it is more likely to respond to medication; if the depression is not severe (ie, more likely to resolve itself) prescribing medication may or may not be effective. But NOT using medication until the patient is shown to be unresponsive to non-medication therapies seems a little cruel.

  6. Harriet Hall says:

    The Mental Health Clinic psychologists I worked with in the Air Force used to ask me to prescribe antidepressants for their depressed patients because they had observed that these patients weren’t able to benefit from talk therapies until their depression had started to lift. This is anecdotal and doesn’t rule out a placebo effect, but it is something to think about, and it ties in with Dacks’ point.

  7. BlazingDragon says:


    You forget side effects (anti-depressants have a lot of side effects, sometimes related to sexual function). It’s not cruel to withhold them (necessarily). Such a judgment needs to be made by the doctor on a case-by-case basis.

  8. Thanks for all the helpful comments.

    I agree that Kirsch appears to have an agenda, and readers can take that for what it is worth. I wanted to just analyze the study at face value.

    I am not advocating withholding medication from those it may help. Medical intervention is always about risk vs benefit, and often we take a stepwise approach to problems, starting with more benign interventions and then escalating as necessary. This information may adjust the risk vs benefit analysis for clinicians, especially since I think the publication bias issue is a real one.

    However I also think the evidence is sufficient to conclude that antidepressants do work, but they have to be used appropriately. And I completely agree with the observation that a primary benefit from medication may be the ability to engage more effectively in therapy, and that in many people therapy may be necessary to lock in real long term benefit. otherwise patients will return to their old patterns of thought and behavior that reinforce the depression/anxiety.

  9. Dacks says:

    “You forget side effects (anti-depressants have a lot of side effects, sometimes related to sexual function). It’s not cruel to withhold them (necessarily).”

    Yes, they do have side-effects. These are powerful drugs and, in my limited experience can save lives IF administered properly. I wonder if there is any information out there on whether the severity of side effects correlates with response to the medication; in other words, if the medication is less effective in less severely depressed patients, are the side effects also less?

    “Such a judgment needs to be made by the doctor on a
    case-by-case basis.”

    Of course. I’m questioning whether medication should be considered only after other therapies have failed. This mode would seem to prolong the disease in many cases. I think most mental health studies show that the best results come from using both drug and non-drug therapies simultaneously

  10. Fifi says:

    Dacks – I’d suggest the problem is trying to find a one size fits all rule/solution regarding depression or any other mental illness. People are unique – biologically, psychologically and in terms of personal history and contemporary context – so the treatment they require will be unique. I’d also suggest that in our advertainment culture (which teaches people they should be always happy or at least look that way so they don’t bother others with their feelings, and then conversely sets out to create anxiety and personal dissatisfaction) there’s a tendency to ignore the fact that sometimes sadness and even some depression can be a normal and healthy response to a situation.

    One of the issues with the prescribing of drugs to treat depression is that sometimes the people prescribing them aren’t really qualified to diagnose or treat mental illness. GPs often don’t have the training for this, and psychologists who may refer patients to a GP for a prescription don’t always have much of an understanding of neurobiology. This, of course, is what happened with the over-prescribing of prozac.

    Dacks – “I’m questioning whether medication should be considered only after other therapies have failed. This mode would seem to prolong the disease in many cases. I think most mental health studies show that the best results come from using both drug and non-drug therapies simultaneously.”

    Well, the problem is that there’s not only been a bias in terms of publishing but also in terms of the kind of research that gets funded so it seems there is no real best evidence approach that can be assumed since there’s a lack of evidence to indicate what’s “best”. Clearly no one is advocating not giving anti-psychotic medication to someone who is psychotic. Or not giving drugs to someone suffering from a deep clinical depression. What’s really being questioned is the efficacy of drugs alone in treating milder forms of depression which very well could be treated by much less invasive means that provide longterm coping and behavioral skills.

    For me the problematic issue with these discussions in general is that they’re lumping all different degrees of depression in together. It’s useful for taking a look at something concrete like how a study is conducted, funded or published, it’s not so useful for coming up with treatment options for actual people – that needs to be addressed case by case.

  11. apteryx says:

    Skeletor and Steven –

    For the benefit of the readers who may be wondering just what “agenda” Kirsch – one of six authors on this meta-analysis – may have: Kirsch’s web site lists CAM among a long series of research subtopics he uses to address his main interests of “response expectancy, suggestion, and suggestibility.” This implies that he is interested in researching CAM effects relating to placebo effects or meaning responses, which is the only effect that the folks around here grant it. Anxiety disorders and depression are among the other subjects listed. He has never published a “study” of St. John’s wort; the only thing he has published that mentions the plant is the following opinion piece:

    Kirsch I. 2003. St. John’s wort, conventional medication, and placebo: an egregious double standard. Complement. Ther. Med. 11:193-195.

    The abstract from PubMed reads as follows:

    “The efficacy of antidepressant medication is generally thought to be well established, whereas that of hypericum (St John’s wort) is considered doubtful. The data fail to support these discrepant conclusions. Instead they show that hypericum and conventional antidepressants are equally effective (or ineffective). This suggests that different standards are being used to evaluate the two types of treatment.”

    Those who are familiar with the record from clinical trials will be hard put to disagree with that. Kirsch did not assert that SJW response is not, at least partly, placebo-based; what he said was that if it is, the same charge can equally be laid against prescription drugs.

    Does this mean that Kirsch is so biased against prescription drugs that he would falsify the results of a meta-analysis, after lining up compliant collaborators to help him do so? I see no evidence of this. Someone who has the opposite “motivation,” of blind trust in the (beneficial) mechanistic effects of any pill being handed out by the pharma reps, would probably never bother to crunch the data to find out how well those pills really work. We do not make ad hominem attacks on the absence of meta-analyses, or on the authors who have failed to write them!

  12. BlazingDragon says:


    The “cookie-cutter” approach doesn’t just apply to psychological disease… most doctors try to apply this reductive methodology to all their patients for most conditions most of the time (it makes their life easier, and that’s saying something in today’s world where a GP’s time is not valued at all). This “cookie-cutter” approach just fails more spectacularly when applied to psychological diseases (because of their inherent heterogeneity (both causes and severity)).

    We need to get back to where doctors have the time to treat patients as individuals and we need to conduct studies that include more people than those who are pre-judged to be most likely to give the result the researchers want (if one is unusual in their physiology, many studies might not apply to them). The problem is, who will pay for both of these approaches? It’s a vexing question in a society that only looks at cost and profit.

  13. Dacks says:

    Well, you can look at using a standard treatment as a “cookie cutter” approach, or you can look at it as the treatment most likely to be effective for the greatest number of people. When a patient is diagnosed with strep throat, the doctor doesn’t individualize his or her treatment, the doctor simply prescribes antibiotics. Now, for a few individuals antibiotics produce a bad reaction, so for them other treatments are sought.

    Similarly, I have gathered from reading articles in lay magazines (I am not a doctor or scientist) and from conversations with mental health professionals that the mode of treatment most likely to relieve depression uses both drugs and cognitive therapy. This is why I question the wisdom of using cognitive therapy without the drugs and only including drugs if the cognitive therapy fails.

    BTW, I agree that GPs are usually not trained in either the proper use of psychoactive drugs or cognitive therapy.

  14. Fifi says:

    Dacks – The thing is, mental health is a bit different and more complex than having strep throat so it’s a bit of a strawman to try to compare the two. Some depression is situational and can be treated entirely through non-invasive means like diet, exercise and cognitive therapy. Prescribing a pill in a situation like this can actually have negative consequences (for instance, diminished sexual desire and emotional awareness could aggravate relationship issues increasing depression). Sometimes it’s about more than just feeling “good”. This isn’t to say that medication isn’t the most appropriate course of action for someone else with a different situation and clear biological basis for depression (such as a bipolar disorder or some other disorder that is contributing to the depression). It’s also important to note that for people with severe depression starting on medications can sometimes pose a suicide risk because it enable the patient enough to kill themselves. In some ways you might as well be saying that everyone should be prescribed placebos because they’ve been shown to have some effect (though obviously this would be unfair and unethical in the case of someone who did need a certain medication).

    Most GPs have enough training to understand psychoactive drugs, they’re just not mental health specialists so they’re not necessarily qualified to diagnose in the same way a specialist is. It’s psychologists who don’t usually have an education in biology and pharmacology (or the right to prescribe), though this has changed over the last decade or so and no doubt is slightly different in different countries (psychiatrists, of course, do have medical training and the right to prescribe). There can be a lot of woo in some types of psychology – it’s actually pretty hard to make generalizations since so many different theories and practices can be called psychology. Psychologists aren’t MDs unless they also trained as MDs. My mother is an MD who also trained as a psychologist (at the time – back in the 70s – she found psychiatry rather sexist and since she was already an MD there was no reason to join the old boys club really and she declined the invitation).

    I’d suggest that the articles you’ve read may well be based upon incomplete evidence since there’s not really enough evidence at this point to make any kind of generalization along the lines that all people suffering from depression should be on medication and engaged in talk therapy.

  15. daedalus2u says:

    It is very easy for lay people who have never experienced depression to not understand it as the serious life threatening disease that it is. Untreated depression has a high mortality rate. The quality of life of people with untreated depression is extremely low. It is the lowest quality of life that a person can have. This can be very hard for some people to understand because the core symptom of depression is the loss of quality of life. The things that make life worth living to most people don’t for people who are depressed.

    Depressed people who attempt suicide are not being irrational or illogical, they are being depressed. When your quality of life becomes sufficiently negative, it is not an irrational decision to try and kill yourself. I am not suggesting that anyone actually do this. I am trying to drive home the point that people with severe depression are not being illogical or irrational, they are being depressed. If you turn the pain of just living up high enough, it just isn’t worth it any more. Treatments with significant side effects are justified in treating diseases with high mortality rates such as depression, or diseases with very low quality of life such as depression.

    To reiterate the point that Fifi made, all effective treatments of depression (not just meds that includes talk therapy) have an increased risk of suicide when they start to be effective. Depressed people need to be watched very carefully during that time to keep them safe.

    As with all diseases, treating it early is better than waiting until it gets worse. It is extremely unfortunate that there is such stigma associated with mental illness. There are many different meds that have different effects on depression, and the effects of the different meds can be quite idiosyncratic.

    I think a big problem in prescribing antidepressants is that there is no real understanding of how they work, and especially how different ones interact. It is known that SSRIs inhibit serotonin reuptake, but no one has ever measured the serotonin level in the synapses of a depressed person. It is not something that can be done experimentally. Synapses are very tiny, the transient is very short, sticking probes into someone’s brain would cause considerable damage (and perturb the synapse anyway), and there are a zillion synapses. A heart doctor would think nothing of prescribing half a dozen drugs to treat a heart condition. The brain is considerably more complex than the heart and much less well understood. I think it is unreasonable to expect a single drug to work, but there is great trepidation in trying multiple things simultaneously. I am pretty sensitive to how my brain is functioning, and the way my doc and I figured out what to try was to take something that worked pretty well and look at the profile of side-effects, figure out which receptors were being up or down regulated, then try another antidepressant that had a side-effect profile that would tend to counteract the side effects of the first med and try it starting out at a very low dose. That heuristic worked very well and it was only then that I realized just how depressed I had been my entire life because I actually felt good.

    Depression is quite interesting to me in the context of my NO research. I have been depressed my whole life, even as a child, and have been on antidepressants for 24 years. Multiple different ones, typically they would work for a while and then stop working. Since I increased my NO level my depression has been better than it has ever been. Increasing my NO did more for my depression than any meds, or more than 25 years of psychotherapy. I now see depression as the necessary aversive state brought on by metabolic stress (actually low ATP in the brain) between the “normal” state and the euphoric near death state which physiology must invoke when you are “running from a bear”. That state must be euphoric and where you have the delusion that you can run forever because if you stop to rest the bear eats you. I think that is also the manic state of bipolar, and the euphoria induced by stimulant drugs of abuse and also the euphoria of autoerotic asphyxiation. I think that vascular depression is also depression caused by low ATP, and the reason that white matter hyperintensities are sometimes associated with it is due to conservation of ATP due to metabolic insufficiency (white matter hyperintensities are due to reduced entrainment of water by axonal transport, shut down to conserve ATP). I appreciate that this is an “anecdote”, but for me it is quite compelling.

    I discuss some of the details in my blog post on the physiology behind the resolution of autism symptoms with fever.

  16. Dacks says:

    “I’d suggest that the articles you’ve read may well be based upon incomplete evidence since there’s not really enough evidence at this point to make any kind of generalization along the lines that all people suffering from depression should be on medication and engaged in talk therapy.”

    Actually, I was stretching a bit: my opinion is based in large part on discussions with my father (an MD), my mother, (a psychologist), and the psychiatrist who treated my husband for severe depression. Again, even though one-size may not fit all (as in the patients who are allergic to penicillin), I am willing to bet that you would have a hard time finding a mental health professional who does not use drugs and talk therapy in combo for a large percent of their patients.

  17. Aaron S. says:

    “depressed people who attempt suicide are not being irrational or illogical, they are being depressed. When your quality of life becomes sufficiently negative, it is not an irrational decision to try and kill yourself.”

    Possible, though they could also have mania or serious false beliefs. But I agree with you that it being a rational act is perfectly plausible. It can be a reaction to a seriously low quality of life.

    Thanks for the candid sharing of your own experiences. Personally, I have used to be depressed for years (6+, not as long as you), and spent weeks researching was to painlessly (relatively) kill myself without making a mess. I couldn’t find any means that met those criteria and didn’t bring about too much suffering around me. I went to a psychiatrist and ended up being committed. My experience there was unfortunate, however. Most of the faculty, including the main doctor, had very simplistic views of things:
    1) Self-killing and mercy killing are irrational and immoral *no exceptions*
    2) Sex drive is Good *no exceptions* (this came up after I mentioned that the possible sexual side-affects might help me concentrate more)
    3) The meds WILL work, 100% chance; thinking that anything else is *a possibility* is “irrational” pessimism

    Dealing with that only makes things more frustrating.

    Anyway, *in my case* the meds only made me tired to the point of very low functionality (I was already sleeping 6/10th of the time before being on them). I was sleeping the day away all the time. Others, I am sure, have better results.

    After giving up on that, and tried some other things. Ultimately, it appears that simple B12 tables eliminated by severe lack of energy, which increased my productivity a lot, which removed a lot of anxiety gave me more interest in things. After not being depressed anymore I wasn’t sure if I was “not depressed anymore” because I wasn’t (and still am not) entirely sure what “normal” feels like. I feel more fulfillment than suffering, don’t want to kill myself, and am much happier now, so I guess that is “not depressed”.

    This eliminated part of the “triangle” of my problems. The others are poor short-term memory and limerence. I will see a psychiatrist about the them. The later is not really fixable, unless MDs prescribe oxytocin antagonists or other things for bizzare, untested, uses.

  18. Fifi says:

    Dacks – Neat, we have a similar parental configuration (not that it makes either of us doctors! ;-). I still think it’s a bit simplistic to compare treating depression like strep throat (that’s an opinion, feel free to hold your own). Obviously we still don’t have the evidence to be able to prove what best treatment is from clinical trials at this point. It being common practice to prescribe drugs alone (which it is) or a combination of drugs and talk therapy isn’t evidence it’s just the current practices. It may be different where you live but in Canada it’s not uncommon for people to undergo psychotherapy without taking drugs. I’m certainly not against appropriate prescribing of drugs, it doesn’t have to be an either/or thing. I’m glad the combo of drugs and therapy was effective for your husband – clearly that was the right treatment for him.

  19. daedalus2u says:

    Arron S. I have been on many different drugs and drug combinations. They all worked for a while, but later stopped working. What did work the best for me was Zoloft, it also did have the most sexual side effects which were/are quite noticeable. But the better mood is very much worth it. Getting a good relationship with a good clinician is the most important part of treatment. There are many more different meds now that can be tried. Getting enough time with a good clinician so the clinician can get to know you well enough to understand how you are describing your symptoms is important. That is extremely difficult to do with insurance, they just don’t provide enough time.

    The “penny wise and pound foolish” policies are bizarre. They will cover in patient psychiatric stuff, but not once a week out patient stuff that keeps you from needing in patient stuff.

    Having a bad experience with a clinician who isn’t competent enough, or even one who is just not a good “fit” is very problematic. In all that time I have only had 2 therapists and I just stopped seeing one a month or so ago.

    It sounds like there wasn’t the possiblity of a good fit at that facility. Those ideas are nonsense, the signs of very unsophisticated clinicians. There are a lot better therapists than that out there. There are some who do psychopharm consults out patient. Non-MD therapists often use an MD for psychopharm separate from the talk therapy.

  20. Aaron S. says:

    daedalus2u: Heh, the medication I was one was Zoloft! But yeah, I know that trying different meds helps some people. Since I don’t feel depressed at all anymore, I don’t plan on trying anti-depressants, but I can bring it up on my with me next psychiatrist. From what I hear, she tends to give each patient a good deal of time and thought.

    Oh, and remember, sexual side-affects (assuming libido loss) *don’t* bother me. I was briefly on Risperdal before (for some possible light compulsive issues) and I had no sex drive. As I predicted, I didn’t miss it, and wouldn’t if I lost it again.

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