Fluoxetine adverse effects

This report and the conclusions reached are uncertain, but they draw attention to the possibility of an interaction between fluoxetine and itraconazole. Consider this interaction if fluoxetine adverse effects are troublesome. 

Hahn SM, Griffin JH. Comment fluoxetine adverse effects and drug interactions. DICP Arm Pharmaco er 99V) 25, 1273-4. 

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. 

Kranzler HR, Del Boca F, Korner P, et ah Adverse effects limit the usefulness of flu-voxamine for the treatment of alcoholism.] Subst Abuse Treat 10 283-287, 1993 Kranzler HR, Burleson JA, Del Boca FK, et ah Buspirone treatment of anxious alcoholics a placebo-controlled trial. Arch Gen Psychiatry 31 720—731, 1994 Kranzler HR, Burleson JA, Korner P, et ah Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am] Psychiatry 152 391-397, 1995 Kranzler HR, Burleson JA, Brown J, et al Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res 20 1534-1341, 1996... 

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. 

Changing a patient from one MAOI to another, or to a TCA, requires a "wash-out" period of at least 2 weeks to avoid the possibility of a drug interaction. There is evidence to suggest that a combination of an MAOI with clomipramine is more likely to produce serious adverse effects than occurs with other TCAs. Regarding the newer non-tricyclic antidepressants, it is recommended that a "wash-out" period of at least 5 weeks be given before a patient on fluoxetine is given an MAOI this is due to the very long half-life of the main fluoxetine metabolite norfluoxetine. 

For highly potent APIs, profound effects can occur at low ng levels, the adverse effect of ethynylestradiol on fish populations is one example [107]. Another example is the development of resistant bacterial strains induced by the release of antibiotics into the environment [112, 113]. Dome et al. [114] concluded that fluoxetine, ibuprofen, diclofenac, propranolol and metoprolol exhibit relatively high acute toxicity to aquatic species. In addition, due to the inherent properties of these chemicals, pharmacodynamic effects were observed in the heart rate of Daphnia magna for the (3-blockers propranolol and metoprolol. 

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. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

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). 

Another open trial of fluoxetine was reported by Van Ameringen et al. (1993). In this study, 16 subjects with a primary diagnosis of social phobia were entered into a 12-week clinical trial. Treatment started at a dose of 20 mg/day and was increased every 4 weeks, according to clinical response and side effects, to a maximum daily dose of 60 mg. Of the 16 subjects, 10 were considered responders, 3 were nonresponders, and 3 dropped out of the trial as a result of adverse effects related to the medication. The response rate of the different subtypes of social phobia was not reported in this study. 

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]. 

Preskorn SH, Beber JH, Paul JC, et al. Serious adverse effects of combining fluoxetine and tricyclic antidepressants. Am J Psychiatry 1990 147 532. 

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. 

As a results of these studies, clinicians have proposed that switching to reboxetine or bupropion might a useful strategy given that these antidepressants share the ability with desipramine and imipramine to block NE uptake. Nevertheless, only one small open label study has been done to test this possibility ( 365). If bupropion is to be used in patients switched from an ineffective trial of fluoxetine, the dose should be kept low for several weeks to allow for the clearance of fluoxetine and norfluoxetine. Case reports indicate that fluoxetine can elevate levels of the active metabolites of bupropion, which, in turn, could mediate an increase risk of adverse effects (366). 

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... 

In terms of comparative adverse effects, imipramine produces more dry mouth than reboxetine probably because imipramine blocks muscarinic cholinergic receptors as well as inhibiting NE uptake (47,5). Imipramine also produces more tremulousness and hypotension than reboxetine. Consistent with their pharmacology, fluoxetine produces more serotonin-mediated adverse effects than does reboxetine (i.e., nausea, loose stools, and somnolence), whereas reboxetine causes more sympathomimetic adverse effects (476). To date, reboxetine has not been reported to cause an increased incidence of laboratory abnormalities. 

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. 

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