Fluvoxamine

Cardiovascular

A slight, clinically unimportant reduction in heart rate has been reported with fluvoxamine [ , ]. There has been one report of supraventricular tachycardia in a woman with no previous cardiovascular disease, but the association with fluvoxamine was unclear since there was no rechallenge [ ].

Nervous system

In a yearlong study of 31 patients there was agitation, which required withdrawal in two patients early in treatment, dry mouth, tremor, and insomnia [ ]. Increased agitation and insomnia may require the addition of a sedative or hypnotic.

Acute dystonia has been described in association with fluvoxamine [ ].

Seizures have been reported in a predisposed subject given fluvoxamine [ ].

Treatment with serotonin-potentiating drugs in usual therapeutic doses can sometimes produce the serotonin syndrome. There are also case reports of this reaction with single doses of SSRIs (see also the monograph on Sertraline) [ ].

• An 11-year-old boy was brought to the emergency room about 2 hours after taking a single tablet of fluvoxamine (50 mg) prescribed for treatment of attention-deficit disorder. He was also taking benzatropine and perphenazine (dosages not stated). On arrival, he was agitated and unresponsive, with bilateral ankle clonus, muscle rigidity, fasciculations, and profuse sweating. His temperature rose to 39.7 °C. He was paralysed, intubated, and ventilated, after which his condition improved. Two days after admission, he had fully recovered.

The dopamine receptor antagonist properties of perphenazine may have played a part in producing the syndrome in this case.

SSRIs can cause insomnia and daytime somnolence; however, the symptoms seem to reflect a sleep–wake cycle disorder. It is conceivable that disruptions in the normal pattern of melatonin secretion, particularly a delay in the normal early morning fall in plasma concentrations, could be involved in the pathophysiology of these symptoms. The fact that these sleep disorders were seen only with fluvoxamine would also support a role of melatonin (see the Endocrine section below).

Psychiatric

Reports of acute mania and manic-like behavior after treatment with fluoxetine or fluvoxamine have appeared [ , ], but there are not enough data to estimate the incidence.

Endocrine

Fluvoxamine causes increased plasma melatonin concentrations. In an in vitro preparation, melatonin was metabolized to 6-hydroxymelatonin by CYP1A2, which was inhibited by fluvoxamine at concentrations similar to those found in the plasma during therapy [ ]. This effect was not shared by other SSRIs or by tricyclic antidepressants, which do not have prominent effects on melatonin secretion. Whether increased concentrations of melatonin and loss of its normal circadian rhythm might cause symptoms is unclear. However, melatonin is believed to play a role in the regulation of circadian rhythms, including entrainment of the sleep–wake cycle. There have been 10 cases of circadian rhythm sleep disorder associated with fluvoxamine [ ]. All the patients had delayed sleep-phase syndrome, which is characterized by delayed-sleep onset and late awakening. The delay in falling asleep and waking up in the morning was 2.5–4 hours. In nine of the cases withdrawal of fluvoxamine or a reduced dosage led to resolution of the sleep disorder. When the patients were given alternative serotonin potentiating agents, such as clomipramine or fluoxetine, the sleep disorder did not recur.

Serotonin pathways are involved in the regulation of prolactin secretion. Amenorrhea, galactorrhea, and hyperprolactinemia have been reported in a patient who was already taking an antipsychotic drug after starting treatment with fluvoxamine [ ].

Three cases of fluvoxamine-induced polydipsia, attributed to the syndrome of inappropriate ADH secretion (SIADH), have been reported [ , ].

Hematologic

Fluvoxamine-associated bleeding has been described [ ].

Skin

Toxic epidermal necrolysis after fluvoxamine has been described; although the patient was taking other drugs, the authors concluded that the skin reaction was probably due to fluvoxamine [ ].

Hair

Hair loss has been associated with fluvoxamine [ ].