Fluvoxamine

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).

Abstract: Background It had been suggested that the antidepressant venlafaxine, which inhibits reuptake of both serotonin and (at higher doses) noradrenaline, may result in better outcomes than treatment with selective serotonin reuptake inhibitors (SSRIs). Aims To compare remission rates during treatment with SSRIs or venlafaxine. Method Data from eight comparable randomised, double-blind studies of major depressive disorder were pooled to compare remission rates (Hamilton Rating Scale for Depression score ≤7) during treatment with venlafaxine ( n =851), SSRIs (fluoxetine, paroxetine, fluvoxamine; n =748) or placebo (four studies; n =446). Results Remission rates were: venlafaxine, 45% (382/851); SSRIs, 35% (260/748); placebo, 25% (110/446) ( P < 0.001; odds ratio for remission is 1.50 (1.3-1.9), favouring venlafaxine v . SSRIs). The difference between venlafaxine and the SSRIs was significant at week 2, whereas the difference between SSRIs and placebo reached significance at week 4. Results were not dependent on any one study or the definition of remission. Conclusions Remission rates were significantly higher with venlafaxine than with an SSRI.

Abstract: We recently reported that fluoxetine or paroxetine, two selective serotonin reuptake inhibitors (SSRIs), when administered to rats, increase the brain content of the neurosteroid 3α-hydroxy-5α-pregnane-20-one (3α5α-ALLO) without altering the brain content of other neurosteroids. ALLO (3α5α and 3α5β isomers) binds with high affinity to various γ-aminobutyric acid (GABA) receptor A subtypes and facilitates the action of GABA at these receptors. We hypothesized that the increase of ALLO brain content induced by treatment with SSRIs could contribute to alleviating the anxiety and dysphoria associated with the symptomatology of major unipolar depression. We measured ALLO content in four cisternal–lumbar fractions of cerebrospinal fluid (CSF) before and 8–10 weeks after treatment with fluoxetine or fluvoxamine in 15 patients with unipolar major depression. The concentration of ALLO (≈40 fmol/ml in each CSF fraction of three control subjects) was about 60% lower in patients with major unipolar depression. However, in the same patients, fluoxetine or fluvoxamine treatment normalized the CSF ALLO content. Moreover, a statistically significant correlation (r = 0.58; P < 0.023; n = 15) existed between symptomatology improvement (Hamilton Rating Scale for Depression scores) and the increase in CSF ALLO after fluoxetine or fluvoxamine treatment. The CSF content of PREG and PROG remained unaltered after treatment and failed to correlate with the SSRI-induced increase of CSF ALLO. The normalization of CSF ALLO content in depressed patients appears to be sufficient to mediate the anxiolytic and antidysphoric actions of fluoxetine or fluvoxamine via its positive allosteric modulation of GABA type A receptors.