Case report: Effective Treatment of Cotard's Syndrome: Quetiapine in Combination with Venlafaxine

Abstract

THE PRIMARY SYMPTOM of Cotard's syndrome is a nihilistic delusion. It has been associated with depression,1,2 bipolar disorder,3 and schizophrenia.4,5 We report a case of a 68-year-old woman with Cotard's syndrome successfully treated with quetiapine and venlafaxine. The woman formerly worked in a public institution as a clerk. In 1999, she experienced depressed mood, poor concentration, auditory hallucinations (transient voices with insulting contents) and inability to do her job properly. She was admitted to a general hospital for 1 month. The next three years were characterized by several major depressive episodes. A major depression with psychotic features was impressed due to major depressive episodes and coexisting auditory hallucinations. In June 2004 she was admitted to our acute psychiatric ward due to depressed mood, social withdrawal, poor appetite, guilty feelings and delusions of reference. Initially, sulpiride (600 mg/day) and fluoxetine (40 mg/day) were prescribed. Six weeks later, her depressive symptoms and psychotic symptoms still persisted. Risperidone (4 mg/day) was later substituted for sulpiride. About four weeks later, her psychotic symptoms improved. She was transferred to a rehabilitation ward and held a part-time job. In October 2006, she developed insomnia, guilty feelings, auditory hallucinations and a suicide attempt by tongue biting. She was transferred to an acute ward in December 2006. Fluoxetine (40 mg/day) and haloperidol (15 mg/day) were prescribed for treating the depressive symptoms and auditory hallucinations. Four weeks later, the depressive and psychotic symptoms did not improve. Moreover, she revealed nihilistic delusions (she stated that her buttocks and nose had disappeared) and persistent memory impairment. She scored 16 out 30 on the Mini-Mental State Examination (MMSE). Laboratory test results, including serum electrolytes, chemistry profile, liver and renal function, thyroid function tests, rapid plasma reagin screening test, serum B12, folate levels, HIV screening, chest radiograph and electrocardiogram were within normal limits. Computed tomography of the brain (to exclude an organic cause) showed no essential abnormality. Fluoxetine and haloperidol were discontinued due to unsatisfactory effects. Venlafaxine (150 mg/day) and quetiapine (400 mg/day) were prescribed for four weeks. Initially, the medications did not relieve her depression and delusion. For the purpose of treating depression and psychotic symptoms simultaneously, the venlafaxine and quetiapine dosages were increased to 225 mg/day and 600 mg/day, respectively. Two weeks later, the depressive symptoms and nihilistic delusions were alleviated. In March 2007, she was transferred to a rehabilitation ward. Following this her cognitive function improved markedly and her MMSE score increased to 26. Her mood has been euthymic and she has been free from positive symptoms of psychosis. This is the first report demonstrating a combination of quetiapine and venlafaxine in the treatment of Cotard's Syndrome. In this case, the subject displayed miscellaneous psychiatric symptoms in addition to the typical nihilistic delusions. The diagnoses of schizophrenia and schizoaffective disorder were not justified because the hallucinations and delusions occurred only during major depressive episodes. She experienced memory impairment but the results of laboratory tests were within normal limits. The memory impairment subsided when the patient recovered from depression. The memory impairment may have been due to the depression condition (pseudodementia). In previous reports,4,6 patients with Cotard's syndrome were treated with antipsychotics and there was only a partial response. Our patient had a good response while using quetiapine and venlafaxine. Her psychotic and depressive symptoms almost completely disappeared. Clinical studies revealed that quetiapine was effective as augmentation of selective serotonin reuptake inhibitor/venlafaxine therapy in patients with major depression.7 Some researchers proposed a possible mechanism for quetiapine in treating depression when combined with venlafaxine.8 The effects may be due to the synergetic action of combined treatment to increase neurogenesis and brain-derived neurotrophic factors expression in the hippocampus, which is reduced in volume among patients with depression or schizophrenia. It is necessary to further study the treatment and underlying mechanisms of this disorder. Received 5 July 2008; revised 24 August 2008; accepted 1 September 2008.