14 December 2009

SSRIs: Personality 1st, Depression 2nd?

Selective serotonin reuptake inhibitors (aka SSRIs) are widely prescribed as anti-depressants, and are also sometimes prescribed as a kind of anti-anxiety drugs. Since clinical depression and anxiety disorders are among the most common mental health conditions, SSRIs (like Paxil and Prozac) are among the most important psychiatric drug treatments.

A new study suggests that SSRIs address depression by changing personality traits that are linked to serotonin levels.

As their name suggests we have a reasonably decent understanding of how these drugs work at the biochemical level. Serotonin is a key chemical in the brain (it also serves different roles in other parts of the body). Some parts of your brain put some of these key chemicals into your brain, and others suck them out so that your brain doesn't get flooded with them. The process of sucking excess brain chemicals out of your brain is called reuptake. By inhibiting reuptake of serotonin in your brain, SSRIs leave more of serotonin floating around in your brain doing whatever it is that it does.

It has long been known that SSRIs can end severe depression. It has also long been known that SSRIs impact "big five" personality traits; they substantially lower neuroticism and increase extraversion.

High neuroticism involves a tendency to experience negative emotions and emotional instability. Low extraversion refers to a lack of sociability, assertiveness and upbeat feelings. Both of these personality traits have been linked to the action of a chemical messenger in the brain called serotonin.


High neuroticism and low extraversion are risk factors of depression. The new small study, of 240 depression patients, found that:

Depressed patients taking Paxil reported much greater change in these traits, as assessed via scores on personality tests, than patients given placebo pills. The difference was notable even after accounting for the extent to which each treatment diminished standard measures of depression. . . . Patients who experienced especially pronounced personality change during four months of Paxil treatment displayed a particularly low depression relapse rate over the next year of treatment. . . . As in earlier studies, placebo patients reported much the same depression improvement as did patients receiving either Paxil or cognitive therapy. But on measures of personality traits, Paxil patients reported substantially lower neuroticism and higher extraversion after two months, compared with moderate personality changes for cognitive therapy patients and minimal changes for placebo patients. . . . Drops in neuroticism scores in patients undergoing cognitive therapy did not predict lower relapse rates. Personality changes during cognitive therapy may arise as a by-product of diminishing depression[.]


A large 2004 twin study suggests that "the genetic factors underlying [big five personality trait] neuroticism are nearly indistinguishable from those that influence liability to [the psychiatric diagnosis] generalized anxiety disorder. Similarly, a 1989 study concluded that "a very high proportion of' the reliable [i.e. non-measurement error derived] variation in anxiety and depression symptoms is due to the same common factor measured by the [Neuroticism] scale[.]" An analysis of the 1989 study and other studies in 1991 argued that:

Short-term changes apart--which contribute to specific environmental variation--virtually all the environmental variation in Neuroticism and scores on . . . Anxiety and Depression . . . has a general effect on all scales. Long-term environmental effects contribute to all traits simultaneously. That Neuroticism, Anxiety, and Depression are not completely correlated is probably due to short-term fluctuations rather than to an underlying difference in the genetic basis of the traits. . . . [N]euroticism . . . is highly heritable in both sexes. Anxiety and depression are far more influenced by environmental effects, some of which precipitate the expression of depressive symptoms without affecting anxiety.


The personality trait neuroticism and clinical psychiatic generalized anxiety, may be part of the same phenomena. And, the way that SSRIs work suggest that the genes that impact these conditions may have something to do with serotonin level regulation.

These studies suggest that SSRIs may actually be anti-anxiety drugs first, and anti-depressant drugs second, rather than the other way around. Understanding this mechanism could help clinical mental health providers distinguish between people who are likely to benefit from SSRIs and those for whom other kinds of treatment would be more effective.

This study also contributes to a growing literature that is helping us to link brain chemistry, the psychology of personality, and framework used to diagnosis psychiatric disorders into a coherent, evidence based whole. Given that an important part of the anti-psychiatry movement and more constructive criticism of the psychiatry field hinge of the taxonomy issues that go into diagnosing mental health conditions, these are important advances. One of the Holy Grails of the mental health field is to develop the equivalent of a periodic table of the elements that links mental health conditions to their causes in an organized way.

No comments: