Association of Paroxetine with Suicide Attempt in Obsessive-Compulsive Disorder

Findings indicate that a decreased serotonin metabolism in the brain is related to aggressive or suicidal behavior (Apter et al., 1991; Mann et al., 1999). There are also some pharmacological indications that agents enhancing serotonergic transmission, for example selective serotonin re-uptake inhibitors (SSRI), may be effective in treatment of suicidal behavior. In a double-blind study, paroxetine appeared to be effective in the prevention of recurrent suicide attempts in a subgroup of patients who had attempted suicide more than once, but who did not suffer from major depression (Verkes et al., 1998). In contrast, depressed patients who experienced intense suicidal ideation after having started or increased the dose of the SSRI fluoxetine have also been described (Power et al., 1992; Teicher et al., 1990). The following case report is intended to contribute to the discussion of the different aspects of theoretical considerations, results of controlled trials and single case reports about the connection between suicidal behavior and SSRIs. Here, we report on a non-depressive who tried to commit suicide after administration of paroxetine for five days. The case was observed within the AMSP (Arzneimittelsicherheit in der Psychiatrie) study, which is a drug safety project in Germany and Switzerland wich the aim, amongst others, of detecting unknown or unexpected adverse drug reactions in psychiatric inpatients (Grohmann et al., 1999).

Mr. M., 32 years old, had already suffered from obsessive thoughts and impulses for twelve years (diagnoses: Obsessive-compulsive disorder ICD 10: F42.0; DSM IV: 300.3). In 1996, he was admitted to our hospital for the first time, and was treated against his obsessions with clomipramine (175 mg/d), which he terminated on his own about half a year later. The following year he was again admitted to our hospital due to an increase in aggressive obsessive impulses to hurt other people. No reason was found for the deterioration. Mr. M. was a little restless and dejected, but not really depressed. Psychopathology included weak suicidal thoughts, but he was clearly detached from realization. He had never attempted suicide in the past. Mr. M. had been abusing alcohol for three years; recently, he had been drinking 1.5 liters of beer a day. Glutamyltransferase 83 U/l (norm below 28) and glutamic pyruvic transaminase 29 U/l (norm below 22) were both increased, pointing to alcohol-related liver damage. But, in the course of hospitalization, no typical alcohol withdrawal symptoms, such as tachycardia, sweating or hand tremor, occurred. The physical examination, the electrocardiogram and the electroencephalogram were normal. Before his admission to hospital, he had not taken any kind of medication. After hospitalization, he was given promethazine in daily doses of 150 mg and on the third day additionally lorazepam 1.0 mg due to his restlessness. On the fourth day of his hospitalization, he was given 10 mg of paroxetine, and from the fifth day onwards, he received a daily dose of 20 mg of paroxetine against his obsessions. On the first day after taking paroxetine, he reported nausea, a strong sense of guilt, aggression, fear of losing control and increasing restlessness. On this day, he was given 100 mg of promethazine and 5 mg of lorazepam for his agitation. On the second and third days, he was given 200 mg and 150 mg of promethazine, respectively. After an application of paroxetine for four days, his suicidal thoughts increased and he was transferred to a closed ward. He feared that he could give way to his obsessive impulses and kill other people. He also had thoughts of killing himself. On this day, he was given 150 mg of promethazine, 75 mg of levomepromazine and 2.5 mg of lorazepam in addition to paroxetine. The next morning he tried to commit suicide by jumping off a wall of 2.20 m height. He sustained injuries at the head and a distortion of the cervical spinal column. The paroxetine medication was terminated. He was then treated with risperidone as an alternative therapy for obsessive-compulsive disorder (Jacobsen et al., 1995). Three weeks later Mr. M. was discharged from hospital. He was given a prescription of risperidone 6 mg/d and promethazine 150 mg/d and no longer suffered from suicidal thoughts or intense restlessness. His obsessive impulses had also improved.

Neither controlled trials (Verkes et al., 1998) nor metaanalysis (Beasley et al., 1992) support the supposition that SSRI predisposes the deterioration of suicidal ideation in non-depressed patients. However, even large, controlled investigations may fail to detect rare but clinically important adverse events (Healy et al., 1999; Power et al., 1992). Often, various groups of patients, including those with a high risk factor of harming themselves, are excluded from drug trials. The data of a review of 13 follow-up studies suggest that obsessive-compulsive disorder does not involve an increased risk of suicide (Goodwin et al., 1969). For reasons of temporal coherence, we suppose that the suicide attempt of Mr. M. was, at least partly, induced by paroxetine. An alternative explanation could be the spontaneous worsening of his illness or of bis symptoms by an alcohol withdrawal, but vegetative parameters were stable. Presumably akathisia or akathisia-like activity produced by SSRIs plays a key role in worsening suicidal behavior in some patients (Müller-Oerlinghausen et al., 1999; Power et al., 1992; Wirshing et al., 1992). Our patient showed no real akathisia, but an increase in restlessness was prevalent. Maybe a benzodiazepine withdrawal could have caused the restlessness, but Mr. M. only received lorazepam four times before he tried to commit suicide. It may be possible that the combination of a worsening of his illness with obsessive impulses and the effects of paroxetine led to symptoms such as aggression, fear of losing control and increasing restlessness, and may have provoked his suicide attempt. The decisive mode of effect of paroxetine might be a partial loss of impulse control, similar to reports about disinhibition of libido by SSRIs (Greil et al., in press). The purpose of this report is to inform about the possibility that not only fluoxetine but also paroxetine may provoke suicidal behavior, and not only in a small number of depressive patients, but also in individual patients with obsessive-compulsive disorder. Whether or not SSRIs impose risks different than classic tricyclic antidepressants in increasing suicidal tendency in susceptible patients is to be clarified, for example within the AMSP project.

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