Violent acts associated with fluvoxamine treatment

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine have been associated with suicide attempts and violent acts.^1,2 We report 3 female patients with refractory panic disorder who, during fluvoxamine treatment, impulsively hit family members.

Case 1

A 32-year-old woman experienced abrupt onsets of palpitations and shortness of breath during the last 9 years. She could not enter reinforced concrete buildings or ride on elevators because she had a fear of closed spaces, and she could not go out alone because of anxiety regarding her next attack. This concern was associated with the development of avoidant behaviour. She was diagnosed with panic disorder with agoraphobia and was first treated, unsatisfactorily, with 25–75 mg of clomipramine and several anxiolytics daily because of anticholinergic side effects.

The woman gradually became depressed and was administered 20 mg of fluoxetine and 5 mg of bromazepam daily for 2 months; her medication was then changed to 40 mg of fluoxetine and 1.5 mg of lorazepam daily for about 6 months. However, this medication regimen did not completely suppress her panic attacks or ameliorate her depressive symptoms. The woman was then prescribed 50 mg of fluvoxamine and 2 mg of ethyl loflazepate daily for 1 week, and the fluvoxamine dosage was increased weekly to 150 mg/day. Six weeks after the initiation of fluvoxamine, the woman became irritable and aggressive, and she expressed impulsive violence during disagreements with her husband and mother. Two days after the fluvoxamine dosage was decreased by half (to 75 mg/day) and coadministered with 20 mg of fluoxetine, the abnormal behaviour stopped.

Case 2

A 29-year-old woman began to experience sudden palpitations and shortness of breath when she cleared snow from the front of her house 3 years previously. She sometimes had to be taken to hospital by ambulance when she had a panic attack and would not go out alone because of her fear of the next attack. She was diagnosed with panic disorder with agoraphobia, which was unsatisfactorily treated with 50–75 mg of amoxapine, 25 mg of trazodone and 2–3 mg of ethyl loflazepate, daily, for 6 months. She gradually became depressed and was prescribed a regimen of fluvoxamine (up to 150 mg/day) with coadministration of amoxapine and ethyl loflazepate. After 2 months of treatment, her panic attacks had been, to a large extent, alleviated. She could even ride on the subway alone. However, she gradually began to exhibit signs of irritability and nervousness; she became easily excited when she argued with her husband and was impulsively violent with him. The woman was admitted to a psychiatric hospital for 1 week. Fluvoxamine was discontinued, and 75 mg of amoxapine, 200 mg of sulpiride, 3 mg of ethyl loflazepate and 5 mg of bromazepam was initiated. With this change, the woman's irritability was alleviated and the violence stopped.

Case 3

A 28-year-old divorced woman with a 10-year history of episodic obsessive–compulsive disorder (OCD) had been experiencing palpitations and shortness of breath since she was 23 years old. A recurrent fear of an explosion forced her, when outside, to walk in the centre of the street. She was diagnosed with OCD and panic disorder with agoraphobia, which was unsatisfactorily treated with 100 mg of sulpiride, 20 mg of amoxapine and 0.8 mg of alprazolam or with 50 mg of dosulepin, 10 mg of prazepam and 2 mg of ethyl loflazepate for about 6 months. When the woman became depressed, she was given 50 mg of fluvoxamine daily, with coadministration of 30 mg of amoxapine and 2 mg of ethyl loflazepate. Fluvoxamine dosage was increased weekly up to a maximum of 150 mg/day. After a month on this regimen, she exhibited signs of irritability and aggressive behaviour, expressing impulsive violence toward her mother. Fluvoxamine treatment was discontinued; sulpiride, mianserin and bromazepam were initiated, and the woman's abnormal behaviour ceased.

Discussion

All 3 cases of refractory panic disorder were associated with depressive symptoms. Tricyclic antidepressant treatment was unsatisfactory because of anticholinergic side effects, but it ameliorated the patients' symptoms to a certain extent. When fluvoxamine was coadministered with ethyl loflazepate or small doses of amoxapine for 1–2 months, patients exhibited signs of irritability and impulsive aggressive behaviour. No other antidepressants used in these cases induced such behaviour. Prompt discontinuation of fluvoxamine in cases 2 and 3 and the reduction of fluvoxamine by half and coadministration of fluoxetine in case 1 reversed the symptoms. In case 1, fluoxetine treatment did not elicit the aggressive behaviour that treatment with fluvoxamine did.

Serotonergic abnormalities have been proposed as a neurobiological basis for aggression and impulsivity.³ The aggressive behaviour in these cases may be related to the fact that fluvoxamine is a more selective serotonin reuptake inhibitor than fluoxetine.⁴ Some reports have described the beneficial effect of SSRIs on impulsivity and aggression.^5,6 However, we wish to draw attention to the emergence of paradoxical effects such as impulsivity and aggressive behaviour induced by fluvoxamine treatment.

Fumihiko Okada, MD

Sapporo, Japan

Kiyoko Okajima, MD

Sapporo, Japan