A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression.

This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.

[Psychiatric manifestations of lupus erythematosus systemic and Sjogren's syndrome]. / Troubles psychiatriques du lupus érythémateux disséminé et du syndrome de Gougerot-Sjögren. A propos d'une observation d'un syndrome de Gougerot-Sjögren secondaire associé à un lupus érythémateux disséminé.

UNLABELLED: We present one case of Sjögren's syndrome (SS) secondary to systemic lupus erythematosus (SLE) with predominant psychiatric manifestations, treated with success by cyclophosphamide. From this case, we review the psychiatric aspects of these two autoimmune diseases as described in the literature and we present the etiopathogenic hypothesis and treatment of the psychiatric disorders. Case report--In August 1996, a 38 year old man was admitted in our psychiatric department for agitation. Primary SS had been diagnosed in July 1996. He had previously attempted to suicide but was never hospitalized in a psychiatric department. During the hospitalization in our department, the patient had auditive hallucinations and felt persecuted. He received loxapine 400 mg/day and was remitted in a few days. He was discharged to a convalescent home with the diagnosis of brief psychotic disorder. In October 1996, he was readmitted to our department for agitation. He had shown agitated behavior and aggression in the convalescent home. There were no hallucinations and no affective disorders. He became calm rapidly and was discharged home a few days later. In November 1996, he was found in a coma by a neighbor. He was admitted to an intensive care unit. The lumbar punction revealed blood cells. Cerebral computer tomography showed subarachnoid hemorrhage. The diagnosis was meningeal hemorrhage due to vasculitis. After regaining consciousness, the patient complained of reduced visual acuity. This was believed to be due to retrobulbar neuritis and the patient's vision improved slightly with corticosteroids. The third hospitalization in our department occurred in February 1997 for depression. The patient had shut himself away for days in his apartment. He had suicidal ideas. His mood improved progressively under fluoxetine 40 mg/day. He was discharged to a convalescent home with the diagnosis of major depressive disorder. The fourth and last admission in our department occurred in June 1997. There were disturbances of memory and orientation. He felt sad and guilty about accusation of sexual abuse on his daughter. He presented typical histrionic symptoms: he had catatonic attitudes only in public areas such as the corridors. Cerebral computer tomography and electroencephalogram were normal. There was no biological abnormality. Signs of confusion rapidly disappeared. He felt better after reintroduction of fluoxetine 40 mg/day. Diagnosis was non-specified depressive disorder, but this episode could be retrospectively seen as delirium. After being hospitalized on these four occasions in one year in our psychiatric department, the diagnosis of his systemic disease was revised by rheumatologists. The patient was diagnosed as suffering from systemic lupus erythematosus associated with secondary Sjögren's syndrome. From September 1997, he received cyclophosphamide 2 g intraveinously per month during 6 months. His vision improved dramatically. His ocular dryness became milder. His mood is now stable. He has not suffered from hallucinations or delusion since. Psychiatric disorders in SLE--During the course of SLE, the occurrence of psychiatric manifestations varies widely from 5 to 83%. They include psychotic disorders, major depressive disorders, subtle cognitive disorders and personality disorders of histrionic type. Etiopathogenic hypothesis are: direct activity of the disease on the central nervous system by autoantibodies (antiphospholipide and antiribosome P autoantibodies) (18, 19) or cytokines (interleukin 2, interleukin 6, alpha interferon) (38, 59), side-effects of glucocorticosteroids and hydroxychloroquine (16) or anxious reaction to a chronic and potentially lethal illness (43, 54). Nevertheless, immunologic and cerebral imagery research suggests that psychiatric disorders are related to vasculitis and non-inflammatory vasculopathy of the small cerebral blood vessels. The management of the patients should include treatment of the disease itself and specific psychotropic treatment. Glucocorticosteroids and especially intravenous infusions of immunosuppressive agents, such as cyclophosphamide, are effective. Psychotropic drugs must be used, making sure to avoid SLE-inducing drugs, like chlorpromazine, carbamazepine and lithium carbonate (19, 20, 45). In addition, psychologic care is essential. Psychiatric disorders in SS--During the course of the primary SS, the occurrence of psychiatric disorders is large as well: from 20 to 70% (47, 61, 62). They are mainly major depressive disorders, anxiety disorders, cognitive disorders and dementia. Brief psychotic disorders and delirium are rare. Etiopathogenic hypotheses are similar as those in SLE, with some differences: antiphospholipide and antiribosome P autoantibodies are not usually found in SS and anti-Ro (SSA) autoantibodies in serum are associated with psychiatric disorders (3-11, 61). According to Drosos et al. (29, 30), psychiatric disorders are explained by psychological distress. This slowly progressive fluctuating disease creates constant discomfort from dysphagia, dyspareunia and functional disability. Some of these manifestations can be treated by corticosteroids and psychotropic drugs. Drugs with anticholinergic side-effects, like phenothiazines, tricyclic antidepressants and hydroxyzine which can enhance the oral dryness have to be avoided. Social and psychological support is important too. DISCUSSION: The diversity of psychiatric morbidity in SLE and SS may be due to differences in patient selection and a lack of uniform clinical criteria. Studies which use standardized diagnostic criteria and control groups don't allow one to come to a conclusion about the relative prevalence of the psychiatric disorders in these autoimmune diseases. This will probably be resolved thanks to the recently published "American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes" (1). Finally, we can ask ourselves if there is a significant number of undiagnosed SLE and SS in psychiatric departments. Two studies report systematic search for SLE in psychiatric patients. In 1992, Hopkinson et al. (39) searched for several autoantibodies in serum samples of nearly 300 hospitalized psychiatric patients. In 1993, Van Dam et al. (65) did the same with more than 2,000 patients admitted to a psychiatric hospital. Hopkinson et al. found 1% undiagnosed SLE, which is much higher than in general population, and recommended to search SLE in every patient with a high erythrocyte sedimentation rate in psychiatric services. Results of the Van Dam et al. study suggest on the contrary, that SLE is not a common cause of admission to psychiatric hospitals. There is no study which report systematic search of Sjögren's syndrome in a psychiatric department. This is probably because most of patients receive or have recently received psychotropics with anticholinergic side-effects which is an exclusion criteria of SS. CONCLUSION: Psychiatrists should keep in mind that SLE and primary SS are potential causes of psychiatric manifestations when examining patients with multiple unexplained somatic complaints and psychiatric symptoms. They should then search for autoantibodies in the serum after careful physical examination. Diagnosis of SLE or SS could lead to a better adapted prescription of corticosteroids and/or immunosuppressive drugs and specific psychotropic drugs, making sure to avoid lupus-inducing drugs in SLE and drugs with anticholinergic effects in SS. The existence of psychiatric manifestations in SLE and SS constitutes an indisputable clinical reality that each practitioner must be able to recognize and treat.