Management. The adverse effects of fluoxetine are shared with other selective serotonin reuptake inhibitors.
Reversible cerebral vasoconstriction syndrome. This syndrome is a rare iatrogenic complication of fluoxetine in patients presenting with headache and ischemia (18). Identification of safe alternative treatments for patients with psychiatric illness who would otherwise be candidates for serotonergic medications is an important consideration for individuals affected by this disorder.
Memory disturbance. Postmarketing studies and isolated case reports suggest that fluoxetine may cause impairment of memory in some patients. Memory impairment that results from fluoxetine treatment usually disappears after switching to another selective serotonin reuptake inhibitor.
Skin rash. In fluoxetine clinical trials performed in the United States, 7% of the patients developed various types of rashes and urticaria. Among the cases of rash and urticaria reported in premarketing clinical trials, almost one third were withdrawn from treatment because of the rash or systemic signs or symptoms associated with the rash. Most patients improved promptly with discontinuation of fluoxetine and adjunctive treatment with antihistamines or steroids, and all patients experiencing these events were reported to recover completely.
Gastrointestinal adverse effects. The most common adverse effect is nausea, which occurs in up to 20% of patients receiving fluoxetine. It is usually mild and transient; vomiting is rare. A tendency to develop diarrhea is possible, which is dose-related and transient. Loss of appetite may occur, resulting in possible weight loss. The weight loss is usually mild and may even be beneficial in overweight patients.
Anxiety and nervousness. In some patients, selective serotonin reuptake inhibitors have been associated with increased anxiety, nervousness, and insomnia. This can be alleviated by dosage reduction or by using benzodiazepines.
Movement disorders. Selective serotonin reuptake inhibitor use has been associated with the development of movement disorders, either due to the drug or due to exacerbation of the underlying condition. Akathisia, dystonia, and bruxism have been reported. Some of these movement disorders were due to the use of neuroleptic comedications in psychiatric patients. Rarely, tremor has been reported with selective serotonin reuptake inhibitors; though, if it persists, it may respond to dose reduction or the addition of beta-blockers. Discontinuation of selective serotonin reuptake inhibitors usually leads to improvement of other movement disorders. Dystonia can be treated with botulinum toxin type A.
The mechanism of these adverse reactions is not fully understood. One explanation is that selective serotonin reuptake inhibitors increase the activity of the serotonergic neural pathways that are diffusely interconnected with dopaminergic nuclei. The serotonergic input to the dopaminergic system appears to be inhibitory; therefore, the net effect of selective serotonin reuptake inhibitors would be movement disorders like those induced by the dopamine antagonist effect of neuroleptic medications. Dopamine depletion can manifest as nocturnal bruxism, which may be prevented by using buspirone, a 5-HT1A agonist that reduces serotonergic activity and increases dopaminergic activity (24).
Hyponatremia. This is due to inappropriate secretion of antidiuretic hormone and may occur with the use of selective serotonin reuptake inhibitors in elderly patients. It usually resolves after discontinuation of the selective serotonin reuptake inhibitor.
Seizures. In United States fluoxetine clinical trials, 0.2% of the patients reported convulsions. This rate is lower than that of seizures associated with tricyclic antidepressants. These can be controlled by usual anticonvulsants.
Disorders of sexual function. Depression is a common cause of sexual dysfunction, and antidepressant medications have also been associated with sexual side effects. Selective serotonin reuptake inhibitors have been associated with delayed ejaculation and inability to ejaculate in men and anorgasmia in women. Sexual dysfunction following selective serotonin reuptake inhibitor therapy is considered likely to be due to stimulation of 5-HT2A postsynaptic receptors. This adverse effect has been exploited for therapeutic effect in erectile dysfunction. A prospective, randomized, double-blind, placebo-controlled study showed that fluoxetine plus tadalafil significantly increased the intravaginal ejaculatory latency time in men with lifelong premature ejaculation when compared to placebo, phosphodiesterase-5 inhibitor tadalafil, or fluoxetine alone (20).
Withdrawal effects. Withdrawal effects of serotonin reuptake inhibitors include anxiety, crying spells, psychomotor agitation, irritability, memory disturbances, confusion, and decreased concentration. These are usually mild following fluoxetine cessation; a patient was reported to develop delirium after abrupt discontinuation of fluoxetine (04).
