Tolerability and safety of fluvoxamine and other antidepressants.

Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity.

Clinical effects of pharmacological variations in selective serotonin reuptake inhibitors: an overview.

Although the selective serotonin reuptake inhibitor (SSRI) class of antidepressants shares a common primary pharmacology, namely the inhibition of serotonin reuptake, their secondary pharmacology is remarkably heterogeneous. Inhibition of serotonin reuptake and the consequent increase in serotonin availability are responsible for the relief of depressive symptoms and for some of the adverse effects of this class of drugs. Transsynaptic effects such as modulation of signalling cascades, gene expression processes and neuroplasticity are also important in the mechanism of action of antidepressants. However, this review shows that secondary properties of the SSRIs may contribute to the differences in efficacy and tolerability between members of the class. For example, fluvoxamine has affinity for sigma(1)-receptors -- a property likely to be responsible for its particular efficacy in delusional depression. By understanding the properties of SSRIs and employing careful selection of agents for individual patients, physicians are more able to tailor antidepressant treatments to their patients' particular circumstances.