Selective Serotonin Re-uptake Inhibitors SSRIs

The selective serotonin re-uptake inhibitors (SSRIs) that are currently available are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. They are widely marketed and are in many countries a major alternative to tricyclic antidepressants in the treatment of depression. The SSRIs are structurally diverse, but they are all inhibitors of serotonin uptake, with much less effect on noradrenaline. They have slight or no inhibitory effect on histaminergic, adrenergic, serotonergic, dopaminergic, and cholinergic receptors (1). 

The major advantages of SSRIs over the tricyclic antidepressants are their less pronounced anticholinergic adverse effects and lack of severe cardiotoxicity. However, some studies have shown some degree of nervousness or agitation, sleep disturbances, gastrointestinal symptoms, and perhaps sexual adverse effects more commonly in patients treated with SSRIs than in those treated with tricyclic antidepressants. SSRIs may also be associated with an increased risk of suicide, particularly in children under 16 (9). 

There seems to be little difference between SSRIs with respect to frequency and severity of adverse effects. The most common adverse effects are gastrointestinal disturbances (nausea, diarrhea/loose stools, constipation incidence 6-37%), nervous system effects (insomnia, somnolence, tremor, dizziness and headache 11-26%), and effects on the autonomic nervous system (dryness of the mouth and sweating 9-30%) (2,10). Weight gain or weight loss have been documented relatively infrequently (2). A high frequency of sexual disturbances has been 

Extrapyramidal symptoms (including akathisia, dystonia, dyskinesia, tardive dyskinesia, parkinsonism, and brux-ism) have been reported in association with SSRIs, especially in the presence of predisposing factors (SEDA-14, 14 12). Current data suggest that SSRIs should be used with caution in patients with parkinsonism (see the monograph on fluoxetine). Concomitant treatment with neuroleptic drugs and high concentrations of SSRIs seems to predispose to extrapyramidal symptoms. Elderly patients and women are also at increased risk. 

It is believed that SSRIs produce movement disorders by facilitating inhibitory serotonin interactions with dopamine pathways. While all SSRIs are potent inhibitors of serotonin re-uptake, they have other pharmacological actions that might contribute to their clinical profile. Sertraline has an appreciable affinity for the dopamine re-uptake site, and for this reason might be presumed less likely to cause movement disorders than other SSRIs. However, there is little clinical evidence to support this suggestion and a case of sertraline-induced parkinsonism has been reported (13). 

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CCOHTA] Canadian Coordinating Office for Health Technology Assessment (1997). Selective Serotonin Re-uptake Inhibitors (SSRIs) for Major DepressionyVdJxll The Cost-... 

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

Selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants are equally effective. Hov/ever, SSRIs tend to have fewer antimuscarinic side-effects and are less cardiotoxic in case of overdosage. SSRIs tend to cause gastrointestinal side-effects. Both SSRIs and tricylic antidepressants exhibit a time lag before the action of the antidepressants becomes effective. 

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

Soomro GM et al Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder... 

Fluoxetine is a selective serotonin re-uptake inhibitor (SSRI). The manufacturers of fluoxetine have published a review of the adverse effects that were noted in 1378 patients who took it for up to 2 years (1). 

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