Sertraline adverse effects

Sertraline hydrochloride has an average half-life of about 26 hours, and mean peak plasma concentrations occur at 4.5-8.4 hours. The dosage is 50-200 mg/day orally. Its major metabolite, /V-desmethylsertraline, is less active than sertraline. Adverse effects are as for the SSRIs in general. 

In a randomised, two-way, crossover study, 12 healthy subjects were given a single 100-mg oral dose of sertraline after taking either cimetidine 800 mg or a placebo at bedtime for 7 days. Cimetidine increased the AUC of sertraline by 50%, the maximum serum levels of sertraline by 24%, and the half-life by 26%. There was a small increase in sertraline adverse effects (not specified) while taking the cimetidine. ... 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Ferrando et al. (1999) conducted an open-label trial of fluoxetine or sertraline in 30 depressed HIV-positive women (including 16 of Puerto Rican or Dominican descent). No differences in treatment response or adverse effects were found between groups. 

Fluoxetine, along with sertraline, fluvoxamine, and paroxetine, belongs to the more recently developed group of SSRI. The clinical efficacy of SSRI is considered comparable to that of established antidepressants. Added advantages include absence of cardiotoxicity, fewer autonomic nervous side effects, and relative safety with overdosage. Fluoxetine causes loss of appetite and weight reduction. Its main adverse effects include overarousal, insomnia, tremor, akathisia, anxiety, and disturbances of sexual function. 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

Paroxetine. Paroxetine, also a serotonin reuptake inhibitor, has been the subject of a case report in two subjects. Ringold [1994] reported the effective treatment of two individuals who had not responded to prior therapy with fluoxetine and sertraline. Both individuals had comorbid psychiatric problems. Subject A demonstrated both social phobia and dysthymia. Although her symptoms of dysthymia were clinically responsive to fluoxetine therapy, her social phobia symptoms were resistant. Subject B had body dysmorphic disorder, obsessive-compulsive disorder, and social phobia. His obsessive-compulsive disorder symptoms benefited from fluoxetine therapy, but his social anxiety was resistant. Sertraline therapy was attempted in both subjects. Subject A required discontinuation because of adverse effects. Subject B experienced a worsening of both obsessive-compulsive disorder and social phobia symptoms. Both subjects demonstrated a positive response in their symptoms when switched to paroxetine [20 mg/day]. 

Di Rocco A, Brannan T, Prikhojan A, et al Sertraline induced parkinsonism a case report and an in-vivo study of the effect of sertraline on dopamine metabolism. J Neural Transm 105 247—251, 1998 Doughty Ml, Lyle WM Medications used to prevent migraine headaches and their potential ocular adverse effects. Optom Vis Sci 72 879-891, 1995... 

Fluvoxamine, fluoxetine, and paroxetine have nonlinear pharmacokinetics, which means that dose increases lead to disproportionately greater increases in plasma drug levels (25). In contrast, citalopram and sertraline have linear pharmacokinetics. For these reasons, dose increases with fluvoxamine, fluoxetine, and paroxetine can lead to greater than proportional increases in concentration-dependent effects such as serotonin-mediated adverse effects (e.g., nausea) and inhibition of specific CYP enzymes. 

In 1988, fluoxetine became the first SSRI marketed in the United States. Since then, sertraline (1992), paroxetine (1993), fluvoxamine (1994) and citalopram (1998) have been marketed. Their widespread acceptance has added substantially to the patient-years of experience with these medications. Thus, the confidence in our knowledge of the adverse effect profile of these drugs in the general population and in special populations (e.g., the elderly, the medically ill) has grown substantially over the past decade. 

TABLE 7-25. Comparison of the placebo-adjusted incidence rate (%) of frequent adverse effects for fluoxetine, sertraline, paroxetine, venlafaxine, and nefazodone... 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

Fluoxetine was the first SSRI to reach general clinical use. Paroxetine and sertraline differ mainly in having shorter half-lives and different potencies as inhibitors of specific P450 isoenzymes. While the SSRIs have not been shown to be more effective overall than prior drugs, they lack many of the toxicities of the tricyclic and heterocyclic antidepressants. Thus, patient acceptance has been high despite adverse effects such as nausea, decreased libido, and even decreased sexual function. 

Fluoxetine is a potential drug of abuse.136 Overdose with sertraline causes suicidal tendencies, whereas citalopram causes fatal reactions such as cardiac dysfunction.137 The adverse effects could be treated with stomach wash, administration of activated charcoal, dialysis, and hemoperfusion. 

Gastrointestinal adverse effects are one of the major disadvantages of SSRIs. The most common is nausea, and the incidence is said to be 20% or more for paroxetine (45,46), sertraline (47), fluvoxamine (5), fluoxetine (48), and citalopram (10,49). Although nausea can lead to drug withdrawal, it usually disappears after a few weeks. Other gastrointestinal symptoms that occur commonly with fluoxetine and sertraline are loose stools and diarrhea (47,48,50), while constipation has been more often reported with fluvoxamine (5) and paroxetine (45,46). 

The ability of SSRIs to cause delayed ejaculation has been used in controlled trials of men with premature ejaculation (61,62). Of the SSRIs, paroxetine and sertraline produced the most benefit in terms of increase in time to ejaculation, but fluvoxamine did not differ from placebo. Clomipramine was more effective than the SSRIs but caused most adverse effects. From a practical point of view many patients might prefer to take medication for sexual dysfunction when needed rather than on a regular daily basis, and it would be of interest to study the beneficial effects of SSRIs on premature ejaculation when used in this way. 

When blood and milk were sampled in 22 nursing women taking sertraline (25-200 mg/day), sertraline and its metabolite, desmethylsertraline, were found in all the milk samples (89). The maximum concentration of sertraline and desmethylsertraline in the milk occurred 8-9 hours after maternal ingestion of the daily dose of sertraline. Eleven infants had detectable desmethylsertraline of these, four also had detectable sertraline. No adverse effects were noted in any of the children. The authors calculated that the infants had received on average about 0.5% of the maternal sertraline dose. 

Sexual disturbance has also been associated with sertraline (14), and a high frequency of such adverse effects has been reported in studies in which high doses were used. In a double-blind, placebo-controlled study of sertraline and amitriptyline in patients with major depression, male sexual dysfunction, mainly ejaculatory disturbance, was reported significantly more often with sertraline (in 21% of the patients) (15). Male sexual dysfunction in 15% of sertraline-treated patients has also been reported (16). 

A 49-year-old man had major adverse effects 11 days after taking a combination of sertraline, buspirone, and loxapine (25). The adverse effects were characteristic of the serotonin syndrome, which is characterized by a constellation of symptoms, including hypomania, agitation, seizures, confusion, restlessness, hyper-reflexia, tremor, myoclonus, ataxia, incoordination, anxiety, double vision, fever, shivering, variable effects on blood pressure, nausea and vomiting, sweating, and diarrhea. 

SSRIs NNRTIs - EFAVIRENZ 1. Possible efficacy and adverse effects, including serotonin syndrome, with fluoxetine 2. Possible 1 efficacy with sertraline 1. Uncertain mechanism possibly bioavailability 2. CYP2B6 contributed most to the demethyla-tion of sertraline, with lesser contributions from CYP2C19, CYP2C9, CYP3A4 and CYP2D6 1. Use with caution consider l dose of fluoxetine 2. Watch for therapeutic failure, and advise patients to report persistence or lack of improvement of symptoms of depression. dose of sertraline as required titrate to clinical response... 

SSRIs ATOMOXETINE t plasma concentrations and risk of adverse effects (abdominal pain, vomiting, nausea, fatigue, irritability) Atomoxetine is a selective norepinephrine reuptake inhibitor, t plasma concentrations due to inhibition of CYP2D6 by fluoxetine and paroxetine (potent), fluvoxamine and sertraline (less potent) and escitalopram and citalopram (weak) Avoid concurrent use. The interaction is usually severe with fluoxetine and paroxetine... 

FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION t plasma concentrations of bupropion and risk of adverse effects Inhibition of CYP2B6 Warn patients about adverse effects, and use alternatives when possible... 

FLUVOXAMINE, SERTRALINE GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects Possibly 1 metabolism Clinical significance unclear... 

BUPROPION 1. ANTICANCER DRUGS - thiotepa 2. ANTIDEPRESSANTS-fluoxetine, fluvoxamine, paroxetine, sertraline 3. ANTIVIRALS - efavirenz, protease inhibitors t plasma concentrations of bupropion and risk of adverse effects Inhibition of CYP2B6 Warn patients about adverse effects and use alternatives when possible. Avoid co-administration of bupropion with protease inhibitors. Co-adminis-ter efavirenz and bupropion with caution. A retrospective study showed that two patients received a combination without reported adverse effects. Potential T risk of seizures... 

PROTEASE INHIBITORS SSRIs t adverse effects of fluoxetine, paroxetine and sertraline when co-administered with ritonavir (with or without lopinavir). Cardiac and neurological events have been reported, including serotonin syndrome Ritonavir is associated with the most significant interaction of the protease inhibitors due to potent inhibition of CYP3A, CYP2D6, CYP2C9 and CYP2C19 isoenzymes Warn patients to watch for t side-effects of SSRIs and consider 1 dose ofSSRI... 

---