This is a topic that gets scant attention leaving the consuming public largely in the dark. Even though I work in the field, I've not hear this information except from my own reading. Fortunately, SSRIs are not as susceptible to problems crossing from brands to generics or between generics. But buproprion in other forms may not be as good as Wellbutrin.

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Antidepressant and antipsychotic drugs have become blockbusters for the firms that developed them, making them hot markets for generic competition. Moreover, the effectiveness of these drugs is measured in the same way as anticonvulsants -- either they work or they don't.

Consequently, psychiatry is another specialty that has had to think about how to handle the variability in potency among generics.

Michael Thase, MD, of the University of Pennsylvania in Philadelphia, said that when problems do arise, it's usually when patients switch between different generic versions of a drug.

"There are multiple generics," Thase said, noting that broad bioavailability confidence intervals allow for substantial variation between different generics.

"If the pharmacy changes generics frequently, which often they do because it's a highly competitive business ... you might have some series of 40% fluctuations," he said. "Every few months there might be such a large fluctuation."

But for antidepressants, clinical problems resulting from these fluctuations are not that common, he said.

The dose-response relationships with SSRIs are not rigid, and, therefore, patients generally don't see big changes in drug effects, he said.

"You might have an increase in side effects with the change, or you might feel you've lost a bit of the therapeutic effect."

But some non-SSRI antidepressants aren't so forgiving, said Jeffrey Lieberman, MD, a psychiatrist at Columbia University in New York City.

He mentioned the tricyclic drug nortriptyline and bupropion (Wellbutrin) as more susceptible than most antidepressants to dosage variations.

In the case of bupropion, he said, seizure risk is relatively sensitive to dosage.

Thase acknowledged that cases do occur when patients suffer serious problems following switches to or between generics. But he said those cases tend to have an outsized influence on perceptions.

"You don't hear about all the times [problems] don't happen," he pointed out. "We may think it's a bigger problem than it is."

Lieberman said the common antipsychotics generally posed few problems with generics.

He said anecdotal reports of problems tended to focus on clozapine. "[It] seems to be a particular compound that suffers from this kind of experience," Lieberman said.

But he cautioned that these reports may result from "the kind of selective memory Michael [Thase] was talking about."

Lieberman noted that it was hard to pin down the potential for problems because -- as is the case with the antiepileptics -- systematic, controlled trials to compare different generic formulations and the branded original are generally lacking.

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Not surprisingly,the biochemical theory regarding "chemical imbalance" is under attack again. The theory has always been an oversimplification of actual research data. All the research has said is that (1) anti-depressants have worked on average slightly better than placebo and (2) anti-depressants and therapy works slightly better than one or the other alone.

Key to understanding what this means are the words "on average", "placebo" and "slightly better". On average, some people did not benefit from anti-depressants, and some did. Some experienced more benefit than others. Anti-depressants, I believe, are over prescribed mainly because clients don't want to invest the time and emotional energy in therapy. People don't want to see themselves as, in part, responsible for their own depression. They'd rather take a pill.

The other part of the confusion is about what is a "placebo". Use of a placebo is a research technique designed to separate the effects of the anti-depressants from all other effects. In anti-depressant research, all the effects of a pleasent psychiatrist, and all of the things a client can do themselves to improve their mood is part of the "placebo". As you can see, a lot of what we all think of as treatment is part of the "placebo". So it is not surprising that there is only a slight improvement in effectiveness of an anti-depressant over "placebo".

Psych Central News

"The chemical imbalance theory, which was formulated in the 1960s, was based on the observation that mood could be artificially altered with drugs, rather than direct observation of any chemical imbalances," Leo said. "Since then there has been no direct evidence to confirm the theory and a significant number of findings cast doubt on the theory."

The researchers said the popularity of the theory is in large part based on the presumed efficacy of the SSRIs, but they say that several large studies now cast doubt on this efficacy.

A review of a full set of trial data published in the journal PLoS (Public Library of Science) Medicine last month concluded that much of the perceived efficacy of several of the most common SSRIs was due to the placebo effect.

Other studies indicate that for every 10 people who take an SSRI, only one to two people are truly receiving benefit from the medication, according to Lacasse and Leo.

Still, the National Center for Health Statistics found that antidepressants are the most prescribed drugs in the United States, with doctors writing more than 31 million prescriptions in 2005.

Both Lacasse and Leo emphasized the importance of patients being given factual information so they can make informed decisions about medications and the role of other potentially useful interventions, such as psychotherapy, exercise or self-help strategies.

"Patients might make different choices about the use of medications and possibly use alternative approaches to their distress if they were fully informed," Lacasse said.

"We believe the media can play a positive role by ensuring that their mental health reporting is congruent with scientific literature."

This research simply says that anti-depressant have, in general, been over prescribed. They can't possibly justify such high use when other viable alternatives, like psychotherapy, are available.

The Wild Moods explains well how the concept of cause and effect is way too simplistic.

In my experience, depression is several pieces of rope, tied up together such that tugging just one tends to tighten the others. Addressing the biochemical is very important, whether through SSRIs or food or amino acid therapy, but it's just one thread, and doesn't in and of itself totally stabilize chronic depression. And in my experience, it certainly does not pull up the roots of the depression, which is more like crab grass than something with a single tap root.

The CDC has released a report finding a spike in successful suicides in adolescents in 2004. This increase is the largest increase since 1990. Is this the result of all the misinformation floating around anti-depressant medications causing suicide and violence in adolescents and adults? Thats about when the hullabaloo started. So that means that the increase in suicides may continue into 2007, four years of increased suicide caused by misinformation in the media. It would appear that media sources who print information on such volatile topics need to consult with professionals before doing so.

Perhaps even more importantly, researchers need to be obtaining peer review of their research before going to the media. It's become routine that new research authors send out news releases on topics that will attract media attention. I'm sure part of this is a survival method to make sure the research sponsor benefits from the research and funds them further. But the consequences of such releases need to be carefully considered.

Note that the research process on the risks of anti-depressants have unequivocally documented that the risk of anti-depressants is less than the risk of not prescribing.

And don't forget that there is also a first line of defense against depression, called psychotherapy. It's harder to face our problems with others, and sometimes more expensive. But it must be done.

Bloomberg.com.

Suicides among children and young adults in the U.S. rose 8 percent in 2004, the largest single- year increase since 1990, the Centers for Disease Control and Prevention said.

The biggest percentage jumps were recorded among girls aged 10 to 19, and boys aged 15 to 19, according to a survey released by the agency today. Suicide accounted for 4,599 deaths in 2004, making it the third-leading killer among Americans ages 10 to 24, behind car crashes and homicides, the research found.

The report, part of an annual analysis by the Atlanta-based CDC, didn't identify a reason for the increase. It found girls mainly hung or suffocated themselves, and that guns remained the primary method used by boys. The rate among Americans ages 10 through 24 had fallen 28 percent since 1990, making the current rise particularly concerning, health officials said.

[..] One possible reason for the increase may be that doctors are reluctant to prescribe antidepressant drugs to children because of warnings about side effects, said Mark Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins Children's Center in Baltimore.

``It's probably reluctance on the part of clinicians to identify and treat kids with depression,'' he said in a telephone interview. ``We know that any treatment for depression in teenagers is quite effective in reducing suicidal thoughts and suicide attempts. When you take away one of the treatments, you are just leaving more kids vulnerable for trouble.''

[..]An earlier study by CDC researchers found many students in the U.S. regularly contemplate suicide. In that survey, 17 percent of high school students said they ``seriously considered'' killing themselves in the previous 12 months and 13 percent actually devised a suicide plan. Nearly 1 in 10 said they actually tried to take their own life.

The decision about how to treat depression has been entirely reframed by recent research. First of all, the debate about whether anti-depressant medications actually contribute to suicidal and other impulsive behavior has called to question routine, first choice prescriptions for Celexa, Lexapro, Prozac, Paxil, and Zoloft, the so-called SSRIs, for even milder forms of depression. Secondly, the STAR*D trials have documented that SSRIs are no magic pill.

SSRIs have been implicated in controversial criminal trials where defendants have claimed the medication made them violent, even homicidal. More recently, research has found a confusing array of results indicating a possible association with increased suicidal impulses in children and adolescents and now adults. However, retrospective studies seem to indicate a weak association of increased suicide attempts only with the younger population.

Unfortunately, the STAR*D trials were designed before the suicide risk with SSRIs hit the newsstands. The research was never designed to assess the effectiveness of medication vs. psychotherapy. However, here is one part of the study that did partly address this question.

NIMH

Switching to or adding cognitive therapy after a first unsuccessful attempt at treating depression with an antidepressant medication is generally as effective as switching to or adding another medication, but remission may take longer to achieve. These results, which are part of the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, are published in the May 2007 issue of the American Journal of Psychiatry.

It seems clear that first choice for treatment of depression is psychotherapy. Persons who are already suicidal or highly dysfunctional with irretrievable consequences to career or key relationships should be considered for anti-depressant medication as well. But it is the clear, there is no justification to treat depression solely with anti-depressant medication.

Anyone taking or contemplating anti-depressants for treatment of depression have been concerned about the blackbox warnings from the FDA. The FDA has issued blanket warnings to anyone considering or taking anti-depressants that they may actually induce suicidal thinking.

The truth is that there is still very little and conflicting information about the risks. Highlighting the risks in the way the FDA did by issuing a blackbox warning has been controversial. The problem is that the risks have been assessed in only a few studies and it is not clear what is happening. The other problem is that anti-depressants also treat and prevent suicidal behavior. Not taking an anti-depressant when you need one can also be a grave risk.

There is concern within the psychiatric and advocate community that the FDA is driven more by politics than science these days. A coalition of psychiatry and advocate organizations has issued an open letter to the FDA pointing to the life and death consequences of their actions.

Psychiatry News

The coalition's "Open Letter on Antidepressants" was released at the coalition's lunch briefing on the same December day that the FDA's Psychopharmacologic Drugs Advisory Committee (PDAC) held a public hearing to discuss the report.

"As advocates for people living with depression and other mental illnesses," the letter began, "we strongly urge the FDA to carefully consider the potential impact of the agency's public statements on the risks and benefits of antidepressants. Access to effective treatments for depression is pivotal in improving the lives of the 19 million Americans that face this devastating illness each year."

The coalition's efforts were led at the December 13 briefing by David Shern, Ph.D., president and CEO of Mental Health America (MHA). He noted that "without treatment, this disorder can be fatal--15 percent of people who live with untreated depression take their own lives.

"Any knee-jerk or pressure-based actions by the FDA may put an untold number of Americans at risk of the tragedy the agency aims to avoid--suicide," Shern stressed. "The risk associated with not treating depression is far greater than any potential risk of adverse effects of medication," he added, echoing his testimony before the PDAC during the public-comment section of the panel's hearing.

As more data emerges about the risk of suicide in the early stages of taking anti-depressants, there appears to be a trend that narrows concern to the very youngest of those prescribed. It also gives a relative sense of the risk by stating incidents as events in a thousand people treated by anti-depressants.

Psychiatr News

FDA's Stone, during his presentation to the panel that morning, emphasized, "The observed relationship between suicidality, age, and antidepressant treatment appears not only in [subjects with] major depressive disorder, but in all subjects with psychiatric diagnoses." One could interpret this finding, he added, as indicating that "[t]here is nothing different in the psychopharmacology of suicide versus the psychopharmacology of depression or another illness--the suicide factor is independent of actual diagnosis."

[...]Risk difference, he explained, "is simply asking the question: How many additional patients--out of 1,000--would you expect to see experience suicidal behavior and/or ideation as a result of taking antidepressant medication?"

From the pediatric data, Levenson said, the answer is 14 out of 1,000 patients under age 18; for those aged 18 to 24, it's 4; and for those aged 25 to 30, it's none-- that is, patients in this age group taking an antidepressant are no more likely to experience suicidal thoughts or behaviors than those not taking such medications.

For patients aged 31 to 64, two fewer patients would likely experience suicidal thoughts/behaviors. For those aged 65 and over, he concluded, "taking an antidepressant prevented 6 patients out of 1,000 from experiencing suicidal thoughts or behaviors."

The risk is clearly focused on the youngest prescribed, those under 18. The risk is sufficient to warrant increased caution for those under 18, but hardly to rule out the use. I think, as with every mental health issue, treat depression starting with therapy. If there is no change in six sessions, then consider adding a medication. If sleep disturbance persists, then a medication review is warranted much earlier. If suicidal behavior is present, an anti-depressant with close monitoring and therapy may be necessary from the beginnings of treatment. Partial hospitalization may be an appropriate alternative for rapid intervention for those who don't present an imminent risk of suicide. Hospitals are not healthy places for people until there is an imminent risk of death or grievous harm to self or others.

Today, I tripped over an interesting article on assessing suicide potential.

Psychiatric Weekly

America bears witness to 30,000 deaths by suicide per year. Although clinicians have a fairly good grasp of long-term risk factors, possible short term indicators of risk have been largely overlooked. Dr. Jan Fawcett believes that, to make real headway in combating suicide, doctors need to identify patients at acute, not just chronic, risk of suicide and treat their symptoms aggressively.

[...]“We have plenty of clinical associations, and even quite a few social and epidemiological associations, for suicide risk,” Dr. Fawcett says. “However, when it comes to a clinician evaluating an individual patient, things can get difficult. Most of the associations we have predict long-term risk for suicide, but clinicians needs to know what’s going to happen tomorrow. When it comes to predicting acute risk, we’re very deficient.”

Dr. Fawcett’s work has suggested that the standard risk factors taught at medical school—prior suicide attempts, suicidal ideation, hopelessness—while strong predictors of ultimate risk, aren’t of much predictive use in the short term. “What I’ve found,” he says, “is that you often see increased anxiety and agitation and severe insomnia immediately preceding serious suicide attempts.”

Dr. Fawcett’s data suggest that increased anxiety and severe insomnia are effective predictors of short-term suicide risk in 70%–80% of hospitalized patients, although he believes the number is somewhat lower in outpatients.

“Patients at high risk are experiencing, through their anxiety and agitation, what I call ‘psychic pain’,” Dr. Fawcett says. “It’s a type of pain I don’t think anyone understands who hasn’t experienced it, but when that’s paired with hopelessness suicide can be the result.” Screening for this type of anxiety is no simple task, Dr. Fawcett explains. “Anxiety is not uncommon in depression— ≥60% of depressed patients have moderate anxiety. The real warning sign is an increase in symptoms of anxiety, but assessing the severity of anxiety goes against the current habit of classifying symptoms as either present or absent. Clinicians need to ask probing questions regarding the severity of the symptoms, and, also, find out how much of the day is spent experiencing the symptoms.” MORE

Dr. Fawcett is correct. I have found the "psychic pain" he's talking about is an existential stress where one's sense of competence and/or value as a human being has been challenged beyond what the person's self-esteem can tolerate. Thus, a imminently suicidal person believes she is no longer worth the air she breaths, the space she takes on earth, nor can her value to others be seen as no less than an annoyance, and as bad as an intolerable burden. A recent grievous loss, such as an close relationship or a job, combined with a number of other stressors, often triggers the crisis.

I've often wondered about those who are suicidal and treated by SSRI anti-depressants. A few have experienced suicidal crises apparently aggravated by the medication. This has created considerable debate about treating children and adults with SSRIs when suicidal.

As I've said before, anti-depressants AND therapy are often helpful in these crises. However, a suicide watch by family and friends may still be necessary during the crises because of the time it takes for the treatment to work.

Complicating the picture is that SSRIs cause significant side effects when first started. The symptoms are similar, but not necessarily the same as what has been called "SSRI Discontinuation Syndrome". Psychiatric Weekly has another article about this issue.

The antidepressant discontinuation syndrome is manifested by a wide array of symptoms. Onset of symptoms occurs shortly after stopping drug or reducing the dose. Common symptoms include dizziness, anxiety, irritability, panic attacks, mood lability, decreased concentration, and insomnia. Nausea, occasionally associated with vomiting, and other gastrointestinal symptoms are frequent.

[...]By rapidly decreasing the efficiency of the primary inactivating system (serotonin reuptake), SRIs initially can cause nausea, which may be blocked with agents that inhibit serotonin (5-HT)3 receptors.15,16 Adaptation to this SRI side effect occurs during initial weeks of treatment along with other changes in neuronal function. Gradual desensitization of autoreceptors during SRI treatment allows serotonin neurons to recover normal firing rates and to progressively increase 5-HT neuronal transmission, perhaps accounting for the delay in onset of their therapeutic effects.

[...]In prospective controlled trials, paroxetine has been found to have the highest incidence of post-treatment AEs compared with other SRIs. Fluoxetine, by contrast, has the lowest reported incidence of discontinuation symptoms, presumably due to the long elimination half-lives of parent drug and its active metabolite.

My experience has indicated that a few people experience very uncomfortable side effects when starting SSRIs. If they are also suicidal, then the experience of the side effects, sometimes extreme "skin crawling" agitation perhaps similar to the clinical syndrome called "akathesia" may well trigger a suicide attempt.

Suicidal clients who are starting SSRIs need close monitoring.

Here is a heads up for everyone taking or considering anti-depressant medication. One study has found a higher incidence of diabetes in high risk pre-diabetic persons undergoing intensive preventative treatment. What is not clear is whether anti-depressant use was associated with previous serious depression. The results could indicate depression and/or anti-depressant use increases the risk of diabetes. Further study certainly is certainly indicated.

Please note, there is NO reason to consider discontinuing your medication based on this study alone. Bring your concerns to your doctor, preferably a psychiatrist.

Well if anti-depressants, in particular SSRIs work, how do they help? Contrary to the ads you see on television, we don't really know. A recently published article outlines the issues.

Although SSRIs are considered “antidepressants,” they are FDA-approved treatments for eight separate psychiatric diagnoses, ranging from social anxiety disorder to obsessive-compulsive disorder to premenstrual dysphoric disorder. Some consumer advertisements (such as the Zoloft and Paxil Web sites) promote the serotonin hypothesis, not just for depression, but also for some of these other diagnostic categories [22,23]. Thus, for the serotonin hypothesis to be correct as currently presented, serotonin regulation would need to be the cause (and remedy) of each of these disorders [24]. This is improbable, and no one has yet proposed a cogent theory explaining how a singular putative neurochemical abnormality could result in so many wildly differing behavioral manifestations.

In short, there exists no rigorous corroboration of the serotonin theory, and a significant body of contradictory evidence. Far from being a radical line of thought, doubts about the serotonin hypothesis are well acknowledged by many researchers, including frank statements from prominent psychiatrists, some of whom are even enthusiastic proponents of SSRI medications (see Table 1).

However, in addition to what these authors say about serotonin, it is also important to look at what is not said in the scientific literature. To our knowledge, there is not a single peer-reviewed article that can be accurately cited to directly support claims of serotonin deficiency in any mental disorder, while there are many articles that present counterevidence. Furthermore, the Diagnostic and Statistical Manual of Mental Disorders (DSM), which is published by the American Psychiatric Association and contains the definitions of all psychiatric diagnoses, does not list serotonin as a cause of any mental disorder. The American Psychiatric Press Textbook of Clinical Psychiatry addresses serotonin deficiency as an unconfirmed hypothesis, stating, “Additional experience has not confirmed the monoamine depletion hypothesis” [25].

[...]The impact of the widespread promotion of the serotonin hypothesis should not be underestimated. Antidepressant advertisements are ubiquitous in American media, and there is emerging evidence that these advertisements have the potential to confound the doctor–patient relationship. A recent study by Kravitz et al. found that pseudopatients (actors who were trained to behave as patients) presenting with symptoms of adjustment disorder (a condition for which antidepressants are not usually prescribed) were frequently prescribed paroxetine (Paxil) by their physicians if they inquired specifically about Paxil [45]; such enquiries from actual patients could be prompted by direct to consumer advertising (DTCA) [45].

What remains unmeasured, though, is how many patients seek help from their doctor because antidepressant advertisements have convinced them that they are suffering from a serotonin deficiency. These advertisements present a seductive concept, and the fact that patients are now presenting with a self-described “chemical imbalance” [46] shows that the DTCA is having its intended effect: the medical marketplace is being shaped in a way that is advantageous to the pharmaceutical companies. Recently, it has been alleged that the FDA is more responsive to the concerns of the pharmaceutical industry than to their mission of protecting US consumers, and that enforcement efforts are being relaxed [47]. Patients who are convinced they are suffering from a neurotransmitter defect are likely to request a prescription for antidepressants, and may be skeptical of physicians who suggest other interventions, such as cognitive-behavioral therapy [48], evidence-based or not. Like other vulnerable populations, anxious and depressed patients “are probably more susceptible to the controlling influence of advertisements” [49].

The Corpus Callosum talks about the physician side of DTCA.

I personally have spent a lot of time in the office, with patients, trying to undo the misinformation contained in DTCA. It bothers me that I have to do that. I would much rather spend the time providing good education, not undoing bad education. I would prefer to not have to deal with direct-to-consumer advertising at all; but if we have to have it, companies really ought to be held to the standards that exist to ensure balance and accuracy.

So all we really know is that SSRIs are a happy pill. But this happy pill does have some interesting recently discovered properties: Antidepressants may boost brain growth!

Serotonin works as a chemical messenger by plugging into special sockets at the tip of brain cells. These serotonin receptors trigger a cascade of events. One of these events, the researchers suggest, is brain regeneration. In other words, drugs aimed at serotonin receptors make brain cells sprout. "Serotonin terminals may be especially prone to regenerative sprouting," Koliatsos and colleagues write. "We propose that this phenomenon ... may be the key structural effect of serotonin antidepressants." MORE

What this really has to do with treating depression is unknown. One can only deduce theoretically that more serotonin receptors is a good thing. Whether such growth is helpful or harmful is unknown.

Sunday I found a disturbing article in a blog that has a good reputation. Dr. Peter Breggin at The Huffington Post wrote about the FDA decision to require a "black box" warning on the anti-depressant medication Paxil because of the risk of suicide in the beginning of treatment. Dr. Breggin is the author of the book Talking Back to Prozac which is highly critical of the anti-depressant medication Prozac. In his post at Huffington's, Dr. Breggin makes statements that appeared designed to attract attention at the expense of misleading the reader.

I've written about the problem with reading articles about mental health in the press. Essentially, reader beware, what you read many be misinforming you. Sometimes misinformation occurs in the interest of selling a publication. Science has it's own issue with chasing the money.

Research is expensive and finding the means to fund it can be difficult. It's also a necessary process to advance a science. Psychotropic medications are extremely expensive to develop and submit to the FDA for approval. The FDA makes the decision to approve a medication based on research completed by the pharmaceutical companies who have a vested interest in the outcome. It's pretty clear that this procedure invites significant inappropriate salesmanship into the research process, but the alternative is likely even more expensive. The only alternative I can imagine would require a large government bureaucracy to manage a process that may be no less fraught with potential for corruption due to the millions of dollars at stake. I can't criticize a system when I can't imagine a working alternative.

Meanwhile, a comprehensive review of all studies of anti-depressant drugs submitted for approval to the FDA showed that when the studies are taken as a whole, anti-depressants don't work.

To support this statement, he sites only two sources when there are literally thousands of articles out there that have different conclusions. Antonuccio et al (2002) makes some quite critical statements about the FDA approval process and questions the magnitude of efficacy of anti-depressant medications. His second source is his own book, Talking Back to Prozac. Antonuccio et al (2002) is not a research study. It is a commentary about a review of the literature in the same publication: Kirsch et al (2002). That particular volume of Prevention and Treatment is full of supporting and detracting articles about the Kirsch et al (2002) study. It's results are universally described as important, but they range in characterization from exaggerated and politically and financially motivated to underestimated.

Most of the articles in Prevention and Treatment Volume 5 note that anti-depressant medications ARE shown effective in the Kirsch et al (2002) study. Even Kirsch et al (2002) conclude anti-depressants are effective, just not as much as one would like to see. One has to keep in mind that drugs affect individuals differently. While on average across large numbers of persons in the study, the magnitude of the drug effect may be relatively small, a sizable proportion of the individuals could have substantial benefit from medication.

Dr. Breggin next makes a statement that implies taking prescribed anti-depressant medications have a following because it gives users a high like recreational drugs.

Of course, many people feel helped by antidepressants, as well as many other psychiatric and even recreational drugs. The placebo effect is enormous. In addition, the artificial euphoria or emotional flattening produced at times by antidepressants may provide temporary relief at the cost of rationality and effective dealing with life.

The uninformed reader very likely would be discouraged from using anti-depressant medications and misinformed that they make a person "high". Not only does this statement misinform and confuse, it adds to the stigma of mental illness by equating anti-depressants to recreational drugs.

Next Dr. Breggin takes the argument to unsubstantiated scare tactics.

It's time to say again what I've been saying for too many years on end. The antidepressants aren't antidepressants. They are more likely to make a person worse than better. More tragically, these toxic agents push many people over the brink into suicide and violence.

He cites no evidence that anti-depressants are "more likely" to make a person feel worse. Even the article he cites says otherwise.

Meanwhile, the antidepressants are very difficult to stop taking. Withdrawal from antidepressants can lead to "crashing," with agitation, violence and suicide. Withdrawal from these noxious drugs should be done slowly with experienced clinical supervision. These drugs are not only unsafe to start--they are dangerous to stop. The best approach to antidepressants: Don't start taking them.

Now Dr. Breggin implies anti-depressants are effectively an addictive drug with a characteristic withdrawal syndrome. There is no evidence of this cited. I've not seen any literature that supports this assertion. In fact, one of the key requirements of an addictive drug is that a person develops a tolerance for the medication requiring an periodic increased dose. My clinical experience has not born this out. Instead, what I've seen across many patients, a life time course of medications requiring occasional adjustments, both up and down or a change to a different drug, typically attributed by the prescribing psychiatrists to changing body chemistry over time and age. That is not even close to the typical abuse pattern of patients addicted to, for example, benzodiazopines where they gradually increase their dose over a relatively short period of time supplementing the prescribed supply with illegally obtained prescription drugs, street drugs and alcohol.

The increased incidence of suicide attempts during the medication trials is of concern. However, what this might be attributed to is unclear. I know from my clinical experience, many people report uncomfortable side effects, including flu-like symptoms and increased anxiety that have been known to make some patients worry about "going crazy". These side-effects may well be enough to induce a suicide attempt in someone who is already depressed and hopeless with suicide ideation.

As I have stated before, medications are an important part of treating depression. But they should not always be the first attempt to intervene. Research has shown repeatedly that psychotherapy and medication used together has consistently the best outcomes. I suggested on April 1,

that the indications for anti-depressants be limited to (1) those people who show neuro-vegetative signs of depression, especially significant sleep deprivation due to insomnia or sleep disturbances and a significant loss of weight due to loss of appetite, (2) a moderate or high risk of suicide as indicated by a lethal and available plan, and (3) after a course of psychotherapy of say six sessions produced insufficient improvement in functional impairments in relationships, productivity at work, keeping up with chores, etc, that the therapist refers the patient to their physician for a medication evaluation.

It appears that the literature agrees with me. In a companion article by Irving Kirsch and Alan Scoboria (2002), the authors offer much the same advice:

In the meantime, what are the alternatives for treating patients? Imagine having a choice between four treatments. Treatment A produces a large therapeutic response but also a large number of adverse effects, including diarrhea, nausea, anorexia, sweating, forgetfulness, bleeding, seizures, anxiety, mania, sleep disruption, and sexual dysfunction. Treatments B and C produce therapeutic responses that are almost as great as those produced by treatment A, but without the adverse effects. In fact, the side effects produced by Treatment B are beneficial (e.g., better general physical health). However, the therapeutic effects of Treatments B and C have been evaluated in relatively few studies. Treatment D has been assessed in many comparative studies, in which it has been found to be as effective as Treatment A in the short term and more effective in the long term. It does not produce adverse effects. Given a choice between these alternatives, which would you choose?

Of course, these alternatives are not merely hypothetical. Treatment A corresponds to SSRIs, and the list of side effects is drawn from those that have been shown to be produced by these medications. Treatment B is physical exercise, which has been reported to have lasting therapeutic benefits in the treatment of major depression. It may be nothing more than a placebo, but if so, it is one with desirable rather than adverse side effects. Treatment C is bibliotherapy, another low-cost treatment with demonstrated effectiveness and little danger of side effects. Treatment D is psychotherapy. As noted by Antonuccio et al (2002), "psychotherapy (particularly cognitive therapy, behavioral activation, and interpersonal therapy) compares favorably with medications in the short term, even when the depression is severe, and appears superior to medications in long-term comparative studies. Given these data, antidepressant medication might best be considered a last resort, restricted to patients who refuse or fail to respond to other treatments.

Part of the problem here is that treatment of depression in a clinical setting contains many components only one of which is medication. To test the effectiveness of a medication, a treatment group receives the medication and a control group receives a sugar pill. Both the treatment group and the control group receive the sort of care that is an integral part of a clinical setting. The part of the treatment that is not mediation is called "placebo". Rehm (2002) describes this placebo. The author lists life events, social support, hopeful expectations, and biochemical changes that accompany treatment and enhance immune function and biochemical balances that facilitate recovery from depression. Rehm also lists spontaneous remission and regression or random fluctuation in the measured factors of depression attributable to the instruments measuring them. These final two factors are essentially improvement that can't be attributed to anything else.

While I understand the argument that without a placebo control, one can never hope to measure the effect of treatment attributable to medication alone. However, imagine if a patient picked up his medication from a grumpy, shaming pharmacist, do you think the medication would be as effective? I think not. The placebo effect is as integral a part of treatment as the medication. It's effects on treatment are not well known.

The other problem is that the typical medication trial used for justifying the approval to the FDA is 6-8 weeks, mainly to contain the costs of research. Anti-depressant medications just come up to therapeutic levels in the blood in the fourth week. From my clinical experience, those four weeks of waiting for the therapeutic levels are quite uncomfortable for the sufferer. The client is waiting for relief from a miserable condition made even more so by the well known side effects of starting and ending anti-depressant treatment. By the end of the fourth week, the clients sense of equilibrium at best is improved but tenuous. Recovery continues over the next few weeks in a stutter-step fashion: one step forward, two steps back, two steps forward, one back. To measure effectiveness in the 6th to 8th week is not likely to show anything more than the beginings of therapeutic effect.

Finally, as demonstrated convincingly in the recently released mega-study of anti-depressants called STAR*D2:

These results highlight the need for longer treatment duration and more vigorous medication dosing than is current practice in order to achieve optimal remission rates. Informed triage or critical decision points (i.e., the discontinuation of patients who experience minimal benefit after 6-9 weeks of treatment) allow for extended dosing for those who are benefiting, while curtailing extended treatment for those who experience minimal benefit after a substantial treatment period. The measurement-based care methods used in this study were easily implemented in actual practice. Controlled trials of this approach in practice are recommended.

And from my previous post on STAR*D2:

The important finding in the STAR*D Part 2 study was that persistence in seeking a combination or a change in medication increased remission rates. If one counts each medication trial as 6-8 weeks and add to this 12 to 16 weeks or more for psychotherapy to address complicating factors like anxiety, a history of mistreatment, abuse or trauma or substance abuse, it's reasonable to expect at least 16 weeks of concerted, persistent and painful effort to make progress with a resistant depression. Many sufferers are tempted to give up after the first attempt at treatment.

There is no reason to discourage use of anti-depressants. There is however reason to be concerned. I think the concern is sufficient to require frequent monitoring by the prescribing physician and consultation by a psychiatrist whenever there is suicide ideation.

I complained to Huffington Post about this article. I encourage you to join me in encouraging Huffington Post to reconsider the content of this article by emailing them here.

Kirsch, I., Moore, T.J., Scorboria, A., Nicholls, S.S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment, 5 (1)

Today there is another rather lousy article about depression and the use of anti-depressants in the Los Angeles Times. They report there is a drop in the use of anti-depressants over the past year.

First came the warning of a possible link between selective serotonin reuptake inhibitors and suicidal thoughts among children and adolescents. Then came a drop in sales — 14% last year compared with the year before. Now research has found that a single medicine typically does not effectively treat depression for most people and that those with depression often stop taking the medicines altogether.

The change is probably correctly attributed to the warnings of suicidal behavior with children and adults. This news and the type of articles I've been finding in the press about depression is spreading a lot of misinformation. Despite that, it is probably good news that the use of anti-depressants has dropped. It's been clear for awhile that many people who had a less than clinical level of depression have been prescribed anti-depressants. Most treatment of depression is by family physicians.

As Medpundit, a family physician puts it:

This is one of the reasons healthcare is as expensive as it is. We spend money trying to smooth away every little wrinkle in life. Grouchy wife or mother? An anti-depressant will even out your moods. Angry young man? Prozac will make you happy. Or at least, it will make you not care.

She also notes that she'd gladly refer all of her depressed patients to psychiatrists, but there aren't enough of them around.

Buried in the middle of the LA Times article is one statement that seems to be missing in most discussions about anti-depressant medication in the press. Researchers have been telling us for many years that clinical depression (not the "blues") is best treated by anti-depressants and psychotherapy. But psychotherapy requires an investment in time and determination to solve the problem. As Dr. Baker of Mental Notes explains:

Lots of folks dont want to pay for psychotherapy -- and neither does their insurance company -- although with a competent doc, this is much more likely to be the appropriate approach to the problems (and, to a lesser extent, the sadness) of everyday living. Partly this is due to the abundance of poor psychotherapy provided by under-trained clinicians going on out there, but I also think it represents a culture intolerant of delayed gratification, as well. And, intended or not, lots of folks have been persuaded by pharmaceutical marketing practices into believing that a pill is, indeed, pretty close to a cure-all.

I have a suggestion that I think could become a new standard of care for depression. I'd suggest that the indications for anti-depressants be limited to (1) those people who show neuro-vegetative signs of depression, especially significant sleep deprivation due to insomnia or sleep disturbances and a significant loss of weight due to loss of appetite, (2) a moderate or high risk of suicide as indicated by a lethal and available plan, and (3) after a course of psychotherapy of say six sessions produced insufficient improvement in functional impairments in relationships, productivity at work, keeping up with chores, etc, that the therapist refers the patient to their physician for a medication evaluation.

What does everyone think?

Enlightenment Bulletin Board :: View topic - Antidepressant Safety Debate May Include Adult Patients

The yearlong debate over whether antidepressant drugs increase the risk of suicide in some children may soon widen to include adults, as English and Canadian scientists are reporting findings from three new analyses of suicide risk in people over age 18 who have taken the medications. The new findings are mixed, and apparently contradictory, and likely to encourage both patient advocates who believe that antidepressants like Prozac have hidden dangers, and manufacturers who insist that the medications are safe, experts said. One of the reports, an analysis of data on antidepressants from previous studies, found that adults taking the drugs were twice as likely to attempt suicide as those receiving a dummy pill or other treatments, but no more likely to complete the act. The two other reports found no significant link between the medications and suicide. Suicide attempts occurred in less than 0.5 percent of the more than 200,000 people included in the three studies.

Though I am not a physician, I am a mental health professional with 20 years of experience providing therapy often consulting with psychiatrists prescribing medications for depression.

DO NOT stop your anti-depressant medication without consulting an experienced physician, preferrably a psychiatrist. Just because this warning is out doesn't mean the medications are dangerous. Each person should evaluate their prescriptions with expert advice.

Sometimes medication works amazingly well, sometimes they are moderately helpful, sometimes they don't seem to help. Anti-depressant medication should be reserved for times with psychotherapy isn't the only answer. Psychotherapy also changes chemical imbalences. Thinking changes chemical balences and imbalences. Medication is helpful only when attempting to change thoughts and feelings isn't enough.

The fact is that psychotherapy is the preferred first method to treat most depression. Someone with thoughts about suicide or unable to function should be considered for immediate anti-depressant medication. A person who is in immediate risk for suicide with a specific plan should be seen in a hospital emergency room or crisis center.

Often the justification for anti-depressants is a period of sleeplessness that results in the person being unable to think clearly enough to benefit from psychotherapy. The responsible therapist will refer a severely depressed client to a physician for a medication review. Severe depression includes serious sleep and eating disturbances (too little or too much) as well as depressed thinking that interferes with daily functioning.

Medication should not be initiated without also initiating psychotherapy. Psychotherapy helps usually within 6 to 20 sessions. These numbers are not absolute, but a guide that indicates a second opinion might be helpful. Today, insurance companies often offer that second opinion by authorizing payment in blocks of sessions the therapist has to justify. Psychotherapy is most effective when short-term or episodic.

For long-term stubborn problems, episodes of 6 to 20 sessions repeated periodically over a number of years is often as effective or more effective than continuous therapy. Continuous therapy sometimes lulls the therapist and the client into a belief system that therapy is necessary even though progress is not made. On-going therapy may be indicated for those who are unable to stay out of the hospital or function adequately without it. Usually, the situation is obvious enough that the insurance company or physician and others involved agree continuous therapy is necessary.

Any psychiatric medication requires periodic review by a physician with extensive experience with the medication. Not everyone will need anti-depressant medication for the rest of their lives.

David E. Johnson, MSW, LICSW
Licensed Independent Clinical Social Worker