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The selective serotonin reuptake inhibitor (SSRI) antidepressant agents fluvoxamine (Luvox®), fluoxetine (Prozac®), paroxetine (Paxil®), sertraline (Zoloft®), Citalopram (Celexa®), and escitalopram (Lexapro®) are commonly used, generally well tolerated, and considered safe, especially compared with the older-generation tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) (Howland & Thase, 2002). Because of their potent effects on serotonin reuptake, SSRIs are associated with various noxious (Masand& Gupta, 1999) and sometimes serious adverse effects (Ener, Meglathery, Van Decker, & Gallagher, 2003). In last month's Psychopharmacology article, I focused on some of the most common and clinically important side effects of SSRIs. In this article, I will review more unusual and serious adverse effects associated with SSRIs.
UNUSUAL ADVERSE EFFECTS
In the central nervous system, the neurotransmitters serotonin and dopamine interact with each other (Rothman & Baumann, 2006). A secondary effect of boosting serotonin is to down-regulate, or decrease, dopamine activity in certain regions of the brain. One area where serotonin and dopamine interact is in the frontal lobes (Levy & Czernecki, 2006).
Apathy
Some patients taking SSRIs (especially at higher dosages) report that although they no longer feel depressed or anxious, they do feel apathetic or "emotionally blunted" (Opbroek et al., 2002). This emotional state feels qualitatively different from sedation or from the anhedonia associated with depression. This type of apathy may be caused by the down- regulating effects of increased serotonin on dopamine in the frontal lobes. Countering this effect by adding drugs that can increase dopamine or norepinephrine activity (or both) might help. Such drugs include bupropion (Wellbutrin®), atomoxetine (Sfratterà®), modafinil (Provigli®), or stimulant medications such as methylphenidate (Ritalin®, Concerta®, and others) or amphetamine (Dexedrine®, Adderall®, and others).
Although alternative SSRIs can be tried, they may have the same adverse effect. A better choice is to switch to an alternative drug from another antidepressant class, such as bupropion, nefazodone (Serzone®), mirtazapine (Remeron®), venlafaxine (Effexor®), or duloxetine (Cymbalta®). Although the serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant agents venlafaxine and duloxetine block serotonin reuptake (and therefore boost the effects of serotonin), they do not seem prone to dopamine downregulation as are SSRIs. Norepinephrine tends to facilitate dopamine transmission. Therefore, the inherent norepinephrine reuptake-blocking effects of SNRIs may tend to oppose or counter the dampening effects of serotonin on dopamine.
Extrapyramidal Symptoms