26 July 2004

First 9 Days Are Critical

This is my 3rd post on antidepressants (the 1st was Depressing Antidepressants and the 2nd was Spitzer Versus Glaxo) since reports broke out early this year that self or externally-directed aggression had been observed not only in adult patients, but also in adolescents and children receiving the same drugs. Claims ranging from increased suicidality and psychological dependence have been reported.

SSRIs are selective serotonin reuptake inhibitors and they are a new class of drugs to treat depression. Since in depression researchers have noted a lack of recipient neuron stimulation at a synapse, SSRIs were discovered to inhibit the reuptake of serotonin and produce a continued neuronal stimulation. Simply put, it tries to prevent one from getting depressed using this mechanism of action. Examples of these class of medicines include:
fluoxetine (trade name: Prozac, Fontex, Seromex, Seronil, Sarafem)

paroxetine (trade name: Paxil, Seroxat, Optipar, Aropax, Paroxat)

sertraline (trade name: Zoloft)

escitalopram oxalate (trade name: Lexapro, Cipralex)

citalopram (trade name: Celexa, Cipramil, Emocal, Sepram)

fluvoxamine maleate (trade name: Luvox, Faverin)
In primary care practice, depression is more commonly encountered than hypertension. This is the case in the US. In a country like the Philippines, it is a neglected disease, as Filipinos would rather keep their miseries bottled up inside than consult a psychiatrist. Besides, antidepressants, like all other "famous medications," are quite expensive and only a select fraction of the population can afford them.

In the wake of reports that intake of these SSRIs may cause people to try to kill themselves, comes a study by Boston doctor Hershel Jick which is published in the latest issue of JAMA (Vol. 292 No. 3, July 21, 2004) that gives us two important conclusions:
One - The suicidal behavior risk is increased in the first month after starting antidepressants, especially during the first 1 to 9 days.

Two - The risk of suicidal behavior after starting antidepressant treatment is similar among users of fluoxetine and paroxetine compared with the risk among users of dothiepin or amitriptyline, which are tricyclic antidepressants --- the usual antidepressants given before SSRIs were discovered.
In my opinion, the first conclusion should alarm us while the second tries to calm us and is somewhat saying, "Hey, don't worry. There's a suicidal risk alright, but it's comparable to the usual risk you have been living with all these years."

But tell me, honestly, do those conclusions sound cool to you?

Just because we are made to realize that the suicidal risk has probably been there with us all along, and very much like the suicidal risk you would get from taking any of the older antidepressants.....makes everything all right?

What do you think?

It is an anxious environment out there wanting more answers and more assurance. The real problem that concerns regulating authorities is the safety of depressed children and adolescents taking the said medications.

The JAMA editorial tells the real score in this problem:
"Sensitivities about research involving children mean that both academics and industry are increasingly wary about carrying out randomized trials in this age group. The paradox, however, is that it is in these vulnerable populations that high-quality evidence is most needed, yet most difficult to obtain. Relying on evidence from studies of adult populations is far from ideal.

"Although it is reasonable to ask questions about the SSRIs and suicide, it is more difficult to answer them. The problem is that depression is unequivocally and substantially associated with suicide and deliberate self-harm. Depression is also unequivocally and substantially associated with the prescription of antidepressants. Thus looking for an association between antidepressants and suicide and/or deliberate self-harm is going to be difficult."

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