Abstract
There is a converging body of evidence implicating the γ-aminobutyric acid (GABA) neurotransmitter system in the pathogenesis of schizophrenia [1]. Zolpidem, an imidazopyridine, is a non-benzodiazepine hypnotic indicated for the short-term treatment of insomnia [2]. A total of 16–30% of patients with schizophrenia experience difficulty in initiating or maintaining sleep, or have non-restorative sleep [3]. We describe a patient whose sleep disturbance in addition to psychotic symptoms improved following treatment with zolpidem.
The patient was a 39-year-old man who had been diagnosed with schizophrenia characterized by auditory hallucinations and persecutory delusions at the age of 22. He was commenced on Risperidone Consta in 2002 and this was increased to 75 mg in 2006 due to residual psychotic symptoms. The patient also reported chronic sleep difficulties characterized by initial and middle insomnia. He was prescribed zolpidem in 2004 after other hypnotics (temazepam) failed. In the past year, the patient began to abuse zolpidem, taking up to 40 mg a day. In this context, zolpidem was ceased 3 months previously. At this time he was not experiencing any psychotic symptoms.
Following cessation of zolpidem, the patient and his family reported worsening paranoia with insomnia. A week prior to admission to hospital, quetiapine 100 mg was initiated but his psychosis and paranoia persisted. The patient was subsequently admitted to hospital. On admission, Risperidone Consta was continued. Quetiapine was increased to 150 mg with chlorpromazine and lorazepam added with no effect. Despite these measures, his psychosis persisted.
A subsequent review of his past history confirmed that the patient's psychosis and sleep disturbance were significantly better on a combination of zolpidem 10 mg with Risperidone Consta 75 mg fortnightly. Based on this, zolpidem 10 mg at night was restarted with no other oral medication. Over the next 72 h, the patient's psychotic symptoms and sleep disturbance improved significantly and he was discharged home 5 days later. At 10 weeks after discharge on the combination of zolpidem and Risperidone Consta the patient reported no psychotic symptoms or sleep disturbance.
In summary, we postulate that zolpidem not only helped with the patient's insomnia but may have had a specific antipsychotic effect. This is based on the deterioration in his mental state, with psychosis following cessation of zolpidem, the failure of other sedating antipsychotics to resolve his psychosis and sleep disturbance, and the resolution of his psychosis within 72 h after zolpidem was reintroduced.
Emerging evidence suggests that deficits in GABA neurotransmission may be intimately involved in the pathophysiology of schizophrenia and a possible pharmacological adjunctive treatment of schizophrenia would be to modulate the GABAergic system using non-benzodiazepine GABAA receptor agonists such as zolpidem [1].
Benzodiazepines, including GABAAαl binding agonist such as zolpidem, have been noted to be effective in the catatonic subtype of schizophrenia [4]. Caution, however, needs to be exercised due to emerging evidence of zolpidem abuse and dependence [5]. There were issues of potential abuse and dependence for the present patient, even though he did not describe specific withdrawal symptoms on zolpidem cessation.
Nevertheless, based on this case report and emerging evidence in the literature, the use of selective GABAA agonists in the treatment of schizophrenia warrants further study.