Paroxetine long-term effects

SSRI/SNRI GAD OCD Panic disorder PTSD Social anxiety disorder Onset worsening side-effects on initiation few long-term effects Relatively safe in overdose (venlafaxine possibly less safe) Well-described more common with paroxetine uncommon with fiuoxetine... 

Because paroxetine is a potent mechanism-based inhibitor of CYP2D6, this type of inhibition yields nonlinear and long-term effects on drug pharmacokinetics, because the inactivated or complexed CYP2D6 must be replaced by newly synthesized CYP2D6 protein. Thus, coadministration of paroxetine with CYP2D6-metabolized medications should be closely monitored or, in certain cases, avoided, as should upward dose adjustment of paroxetine itself. 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

Paroxetine and placebo had similar tolerability, whereas clomipramine was less well tolerated, with more patients withdrawn from treatment as a result of emergent adverse events. Holland et al. (1994) reported on the effects of long-term treatment with fluvoxamine in patients who had completed a double-blind study. Patients who were transferred from placebo to fluvoxamine and those who continued taking fluvoxamine showed continued improvement in efficacy parameters. 

Fluoxetine, paroxetine, fluvoxamine, and citalopram, as well as clomipramine, have been shown in placebo-controlled, double-blind studies to be safe and effective antipanic drugs for shortterm PD therapy. Evidence also is accumulating to suggest that these drugs may be effective for long-term panic treatment, but more data are needed to confirm this. 

SSRIs with shorter half-lives, such as fluvoxamine and paroxetine (qv), have a higher incidence of withdrawal symptoms than long-acting ones, but withdrawal effects have been reported, albeit rarely, after withdrawal of fluoxetine (qv) (SEDA-20, 8) (76) and citalopram (77). Patients taking high doses, long-term treatment, or both are at increased risk of developing withdrawal symptoms (76,78). 

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have been associated with increasing suicidal ideation in some populations of patients. Recent studies have led the British Department of Health to warn physicians against using paroxetine off label. Fluoxetine was specifically exempted from this recommendation. Long-term studies of patients with depression who were treated with fluoxetine have shown it to be fairly well tolerated. Primary adverse effects include nausea (23%), headache (21%), and insomnia (20%). 

The diversity of the SSRIs is evident not only in their chemical structures, but also in their pharmacokinetic profiles. Fluoxetine has an elimination half-fife of 2 to 3 days (4 to 5 days with multiple dosing). The single-dose hah-hfe of norfluoxetine, the active metabolite, is 7 to 9 days. Paroxetine and sertrahne have half-lives of approximately 24 hours. Unlike paroxetine, sertraline has an active metabolite, but the metabohte contributes minimally to the pharmacologic effects. Escitalopram has a half-life of approximately 30 hours. Peak plasma concentrations of citalopram are observed within 2 to 4 hours after dosing, and the elimination half-life is about 30 hours. The SSRIs, with the exception of fluvoxamine, escitalopram, and citalopram, are extensively bound to plasma proteins (94% to 99%). The SSRIs are extensively distributed to the tissues, and aU, with the possible exception of citalopram, may have a nonlinear pattern of drug accumulation with long-term administration. ... 

The involvement of central serotonergic neurotransmission in human ejaculation has been investigated mainly in animal studies. To date, it seems that the beneficial effect of SSRI treatment in premature ejaculation results from 5-HT2C receptor stimulation. Among the SSRIs, paroxetine has been demonstrated to be more effective than clomipramine and the other SSRIs. Moreover, it has been suggested that long-term SSRI administration is much more efficient than short-term treatment. - ... 

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