SSRI Tales

In 23 years of clinical experience prescribing them since they first made the scene, I have found that the type of antidepressant medications called Selective Serotonin Inhibitors (SSRI’s) are, for the majority of patients (with some important exceptions described in the next paragraph), relatively side effect free. Especially when combined with a long acting benzodiazepine tranquilizer such as Clonazepam, they are also highly effective for many patients who have major depression, panic attacks, obsessive compulsive disorder, PTSD, or the extreme emotional hyper-reactivity characteristic of borderline personality disorder.

Just so I don’t have to keep answering the same question, YES, some people do indeed have nasty side effects from them. YES, the drugs can increase suicidal ideation for some patients under some circumstances. YES, they often wreck havoc on sexual functioning. YES, they can have nasty withdrawal symptoms if stopped cold turkey, especially Paxil. YES, they do not work for everyone. But NO, there is not a shred of clinical or experimental evidence to back up Robert Whitaker’s assertion that patients who get better with the meds in the short run are made worse by them in the long run

In my new book I talk about how first benzodiazepines and now antidepressants are being demonized by the drug companies ever since most of the drugs in each class became available (or were about to) as cheaper generic medications. The only antidepressant that is really different that is not available as a generic is Cymbalta, which is technically not an SSRI. (Lexapro and Prestiq are just old drugs in new packages, as per my blog post of June 14).

Cymbalta has been trying to position itself as the drug best for people with chronic pain – but the old antidepressants like Elavil work just as well for that – and for the wastebasket diagnosis of fibromyalgia. (Another disclaimer: just because fibromyalgia is a made-up disease does NOT mean that “neurogenic” pain is not very very real and significant, so please, no nasty missives on that subject).

Back in January, the headline "Antidepressants May Only Be Effective in Treatment of the Severest Depression" was seen in newspapers around the country and even made the network newscasts. It was based on a meta-analysis, which means that the results of several different individual studies were combined.

The headline was sort of true in some ways but was extremely misleading. It is true that a milder type of depression called dysthymia is less likely to respond to drugs than a more severe variety of depression called major depression. Dysthymia tends to involve the thinking parts of the brain more and is usually more amenable to psychotherapy; major depression tends to involve a more primitive part of the brain called the limbic system more and tends to respond better to drugs. Of course there is considerable overlap between the two syndromes because all parts of the brain are highly interconnected, so diagnosis can at times be an issue.

The news stories did not mention psychotherapy at all and left the vague impression that current drugs should not be used much. Maybe doctors should be adding Abilify, just as the commercials say. NOT!

Only six studies were used in this meta-analysis. All of them did a poor job of distinguishing major depression from dysthymia. All six studies compared anti-depressants to placebo (sugar pill) and only tested one drug. Clinically, that is not the way the drugs are used by psychiatrists. Patients who do not respond to one of the antidepressants often will respond to another. Sometimes we have to try three or four before meeting success. There are diminishing returns with each switch, but the total response rate to antidepressants is the sum of the response rate to drug one plus the response rate to drug two, and so on. The type of study I am criticizing makes the drugs look way less effective than they actually are.

Not only that, but in at least one of the studies, the antidepressant was severely under-dosed! Do you think the authors were trying to make it look bad or something?

In my book, I also tear apart an article in the usually well-respected New England Journal of Medicine that purported to show that antidepressants do not work in depressive episodes seen in bipolar disorder. That paper was dishonest as the day is long.

Now comes a brand new attack on  something called the STAR*D study.  The STAR*D study attempted to study antidepressants in the way that clinicians actually use them, rather than the way they are used in studies. It did indeed show that if one antidepressant does not work after the required amount of time, then another should be tried and so on, and if this is done then the total response rate to antidepressants is actually fairly high in properly diagnosed patients with major depression.

The authors of the attack (Psychother Psychosom. 2010;79:267-279) pointed out that “the effectiveness of antidepressant therapies was probably even lower than the modest one reported…with an apparent progressively increasing dropout rate across each study phase."

“We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care,” lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.

In truth, if a study has a lot of dropouts, then it can just as easily underestimate as overestimate drug effectiveness. This is especially true for antidepressants because they must be continued for a few months after remission is achieved, and patients will often quit taking them prematurely precisely because they feel better. They then relapse. It is disingenuous to the utmost to count drop outs as non-responders!

I agree that the Star-D study was poorly designed to determine sustained efficacy, because that was not its main purpose. The initial good results on the patients who did not drop out are pretty much identical to what is seen clinically.

It is important to follow depressed patients very closely and have a therapeutic relationship with them to emphasize the need to stay on the medication for a while. Some patients have also significant psychosocial stressors that they do not tell the doctor about either because no one asked, or because of shame. A doctor has no hope of sorting out antidepressant response from other variables - often difficult under the best of circumstances - if he or she does not know about the psychosocial context in which symptoms are seen. The type of relationship in which such information becomes readily available to the doctor just does not happen in studies.

In general, drop outs in almost all studies are not tracked, so we have no way of knowing how many might relapse.

Two of the authors of the attack paper, H. Edmund Pigott, PhD, and Gregory S. Alter, PhD., are founders of NeuroAdvantage, LLC, a for-profit "neurotherapy" company. This is a company that has products that one can reasonably assume are competition for antidepressants. The company “offers a number of light & sound neurotherapy (LSN) programs designed to decrease symptoms of depression and anxiety as part of an overall treatment plan. Numerous clinical researchers have found that LSN is a robust treatment effective in facilitating profound relaxation and meditative states.” (From their website).

The first SSRI that was FDA approved was Prozac. As mentioned earlier, that was 23 years ago in 1987. Paxil, Zoloft, and Luvox followed soon thereafter. Isn’t it amazing, after all that time, that a whole bunch negative “new “information about SSRI’s is coming out just as they are all going generic?

Of course, I cannot prove that Big Pharma or alternative medicine is behind this.

Certainly, Big Pharma does want as many depressed patients as possible to be put atypical antipsychotics like Abilify while they still have the patents. More frightening potential evidence is that the drug company giant GlaxoSmithKline sat on data that showed that Paxil caused a huge number of birth defects in pregnant rats (teratogenesis) that they had known about since the drug first came out. Now, after twenty years and like magic, this data suddenly has seen the light of day!

Coincidence? You be the judge.