Short reports
J
Psychopharm
Increased libido associated with quetiapine
Journal of Psychopharmacology 20(1) (2006) 125–127 © 2006 British Association for Psychopharmacology ISSN 0269-8811 SAGE Publications Ltd, London, Thousand Oaks, CA and New Delhi 10.1177/0269881106059732
Anuradha Menon St. George’s Hospital, Morpeth, Northumberland, UK. R. Hamish McAllister Williams School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. Stuart Watson School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. Mental Health Unit, Leazes Wing, RVI, Newcastle, UK.
Abstract We report sexual symptoms in a 44 year old man with schizophrenia who was receiving treatment with the atypical antipsychotic quetiapine. The symptoms consisted of an increased drive to masturbate and spontaneous ejaculations at night time. We discuss the potential neuro-chemical mechanisms for this and argue that quetiapine’s unique pharmacological profile may have contributed to the development of his symptoms.
Keywords
Introduction
He was admitted to a general acute psychiatric ward under the Mental Health Act after an assessment by the crisis intervention and treatment service which was triggered by concerns raised by his community key worker of increasing non-compliance with risperidone, worsening of pre-existing symptoms and refusal to engage with services. He had been out of hospital for 6 months. On admission, he was expressing bizarre delusions, mainly of a persecutory nature. He was started on quetiapine at a dose of 200 mg daily, which was increased to 400 mg on day 2 and to 600 mg on day 4, in an oral dose at night. There was partial response in the form of improvement in behaviour and engagement on the ward. However, his psychotic symptoms persisted. The dose was increased to 750 mg exactly 1 month later. This was associated with improvement in his psychotic symptoms and discharge was planned. On the third week of 600 mg of quetiapine, he reported that the quetiapine had ‘changed his sexuality’. The symptoms increased after the dose was increased to 750 mg and on detailed enquiry he reported increased spontaneous ejaculations at night. He also reported an ‘increased need to have sex, especially with myself’. This would happen several times in the night. He also reported an increased need to masturbate during the day. This was the first time that he had experienced such symptoms. His denial of illicit substance use was corroborated by a negative urine drug screen. He was not prescribed any other medication and was not, to the
Sexual dysfunction occurs in as many as 60% of males with schizophrenia and is probably related both to the disorder and antipsychotic drug treatment. It spans a range of aspects of sexual function including sexual interest (desire, libido), sexual arousal (vaginal lubrication and erectile function) and orgasm (Cutler, 2003). Many patients consider it to be as ‘bothersome’ as the symptoms of schizophrenia (Finn et al., 1990). The antipsychotic agent, quetiapine, has efficacy in the treatment of schizophrenia and bipolar disorder and is considered to have a generally favourable side-effect profile (Goodwin, 2003; Srisurapanont et al., 2004). We present a case report of increased sexual drive associated with the use of quetiapine.
Case report The patient is a 44 year old single unemployed male, who was diagnosed with schizophrenia as a teenager. He has a history of multiple relapses requiring admission and subsequent partial response to antipsychotic medication. Over time, he has been prescribed trifluperazine, chlorpromazine, haloperidol, risperidone, flupenthixol and fluphenazine; side effects have included lethargy and drowsiness.
quetiapine, libido, neurotransmitters, serotonin, adrenoceptor, prolactin, dopamine
Corresponding author: Stuart Watson, Mental Health Unit, Leazes Wing, RVI, Newcastle, NE1 4LP, UK. Email:
[email protected]
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Quetiapine and increased libido
best of our knowledge, taking any over the counter medications during the treatment period. Before admission, the patient was not in a sexual relationship and reported little interest in sex or masturbation. He did not welcome the increase in sexual drive. Routine physical examination and investigations were all within normal limits and prolactin levels taken on 750 mg quetiapine at noon were 140 mIU/L and within the normal range for our laboratory. After 4–6 weeks of a dose of 750 mg/day of quetiapine when seen at outpatient follow up, his sexual symptoms had returned to their pre-morbid levels. At 6 months after discharge from hospital, he was still taking 750 mg of quetiapine per day and was maintaining improvement in psychotic symptoms and occupational functioning.
Discussion It is possible to speculate about the cause of the patient’s sexual symptoms. One can conceivably see this as a return of libido as a consequence of treatment of his positive symptoms. Aizenberg et al. (1995) have demonstrated that untreated patients with schizophrenia show reduced libido. However, in our patient despite partial response of positive symptoms – to a level similar to that seen with other medication in the past – similar sexual symptoms have never been previously documented. This raises the possibility that the increased libido may have been a direct consequence of treatment with quetiapine.
Antipsychotic associated sexual dysfunction The sexual side effects of antipsychotics probably arise from a number of different physiological mechanisms, including central nervous system (CNS) specific effects on neurotransmitters, nonspecific CNS effects such as sedation, hormonal effects and peripheral effects of neurotransmitters – particularly serotonin which has vasoconstrictor and vasodilator effects and participates in the normal sexual response through sexual arousal (Cutler, 2003). Case reports of sexual dysfunction with atypical antipsychotics and side-effect data from randomized controlled trials suggest retrograde ejaculation and priapism with clozapine, risperidone and olanzapine (Arnt and Skarsfeldt, 1998; Cutler, 2003). Tran et al. (1997) report data from a randomized controlled trial showing delayed ejaculation in 2.8% of males taking olanzapine compared to 11.5% taking risperidone. There are reports of reduced ejaculatory volume with sertindole (Zimbroff et al., 1997) and reduced libido in almost a third of male schizophrenic patients on quetiapine (Atmaca et al., 2004). Comparative trials suggest that the burden of sexual dysfunction is lower for quetiapine than for risperidone (Bobes et al., 2003; Knegtering et al., 2004) and that clozapine treatment is associated with significantly better sexual functioning, as assessed by frequency of orgasm, enjoyment of sex and sexual satisfaction than traditional antipsychotics (Aizenberg et al., 2001). Increased sexual drive has been less frequently documented. Adverse event data for olanzapine shows that increased sex drive is seen in 0.7% of patients. (Eli Lilly, data on file). We have been
unable to obtain similar data for the other atypical antipsychotics including quetiapine.
Sexual side effects via antipsychotic induced hyperprolactinaemia Conventional and some atypical antipsychotics increase serum prolactin levels through blockade of the inhibitory effect of dopamine on prolactin release from the pituitary. There is convincing evidence that increased prolactin levels cause sexual dysfunction by depressing desire, erection and orgasm (Cutler, 2003). Furthermore, elevation of plasma prolactin also reduces testosterone levels, which is also thought to lead to reduction in sexual activity (Cutler, 2003). Among the newer antipsychotics, risperidone and amisulpiride have been shown to produce robust increases in prolactin levels (Wetzel et al., 1994; Zhang et al., 2004). In contrast, clozapine, quetiapine and olanzapine are reported either to cause no increase in prolactin secretion at all or to increase it only transiently and mildly (Meltzer et al., 1979; Small et al., 1997; Tollefson and Kuntz, 1999).
Pharmacology of sexual side effects Quetiapine has antagonist properties at a number of receptors including 5-HT2A, 5-HT6 and 5-HT7, nor-adrenergic 1 and 2 and relatively minor blockade of D2 receptors (Stahl, 2000). There are therefore a number of potential pharmacological mechanisms for altered sexual drive involving increased libido with this drug. Quetiapine, like olanzapine, risperidone, ziprasidone and clozapine has 5-HT2 receptor antagonist properties. Animal studies have shown that 5-HT2A agonists facilitate sexual behaviour in rats (Nedergaard et al., 2004) whereas 5-HT2C agonists may suppress sexual motivation and arousal (Popova and Amstislavskaya, 2002). The apparently paradoxical finding that antidepressants with 5-HT2 antagonist properties have a better sexual side-effect burden than tricyclic antidepressants or selective serotonin re-uptake inhibitors (SSRIs), and may improve SSRI induced sexual dysfunction (Rudkin et al., 2004), may be explained by differential effects on 5-HT2A and 5-HT2C receptors (Benelli et al., 2004). The effect of quetiapine and other atypical antipsychotics on sexual function may depend on their relative affinity for these two receptors. In common with risperidone and clozapine, but unlike olanzapine, quetiapine exerts antagonist effects at 5-HT7 receptors (Schotte et al., 1996; Stahl, 2000). 5-HT7 agonists have been shown to inhibit sexual behaviour (specifically lordosis) in female rats (Kishitake and Yamanouchi, 2003) and hamsters (Caldwell and Albers, 2002). Therefore 5-HT7 antagonism is a potential mechanism for quetiapine mediated increased sexual activity. Quetiapine and clozapine unlike the other atypicals are antagonists at noradrenergic 2 receptors. The noradrenergic 2 agonist, clonidine has been shown to decrease receptive (lordosis) and proceptive (ear wiggles) behaviour and significantly increase rejection behaviours (vocalization, kicking, boxing) (Meston et al., 1996). This suggests an additional mechanism by which quetiapine may increase sexual drive.
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Conclusion We propose that the relative blockade of 5-HT7, 5-HT2A, D2 and nor-adrenergic 2 receptors in individuals receiving treatment with atypical antipsychotics will determine the sexual side effects of the treatment, and because of the unique pharmacological profiles of quetiapine and clozapine, these drugs will be more likely to engender an increase in sexual activity and drive than other atypical antipsychotics. Further studies to clarify this point and the precise pharmacology of the effect would be helpful.
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