5-HT neurons depicting the impact of an SSRI on 5-HT neurotransmission. The cell bodies of 5-HT neurons are in the brainstem and give rise to 5-HT projections reaching all brain structures. The rectangles on the cell bodies of 5-HT neurons represent the 5-HT1A autoreceptors, and the ones on the terminals represent the 5-HT1B autoreceptors; their disappearance after long-term treatment is meant to illustrate their desensitization. The rectangles on the postsynaptic neurons represent 5-HT1A receptors in the hippocampus that do not desensitize after long-term treatment. The number of zigzags on the axons and dots represent the firing frequency of the 5-HT neurons and the level of synaptic 5-HT, respectively. (Reprinted with permission from Blier P and Ward H. CNS Spectrum 2002;7:148-153.)
sites. The development of these synaptic events shares the time frame of the delayed appearance of the therapeutic benefit of these agents in depression.
With initiation of therapy with an SSRI, some patients describe anxiety or agitation. This can usually be overcome by reducing the dose and titrating upward more slowly. Insomnia can be a persistent activating side effect that can limit therapy or require the addition of a sedating agent at bedtime. Nausea and loose stools are a frequent side effect and may be lessened by taking the medication with food. As many as one-third of patients taking SSRIs may complain of sexual dysfunction, including decreased libido, delayed ejaculation, and anorgasmia. The SSRIs tend to be weight neutral with the exception of paroxetine (Paxil), which is associated with weight gain. No correlation has been made between plasma levels of the SSRIs and efficacy.
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