F K Judd

N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial.

BACKGROUND Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and refractory to treatment. N-acetyl cysteine (NAC) increases brain glutathione in rodents. This study was conducted to evaluate the safety and effectiveness of oral NAC (1 g orally twice daily [b.i.d.]) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period. METHODS A randomized, multicenter, double-blind, placebo-controlled study. The primary readout was change from baseline on the Positive and Negative Symptoms Scale (PANSS) and its components. Secondary readouts included the Clinical Global Impression (CGI) Severity and Improvement scales, as well as general functioning and extrapyramidal rating scales. Changes following a 4-week treatment discontinuation were evaluated. One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were randomized; 84 completed treatment. RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [-5.97 (-10.44, -1.51), p = .009], PANSS negative [mean difference -1.83 (95% confidence interval: -3.33, -.32), p = .018], and PANSS general [-2.79 (-5.38, -.20), p = .035], CGI-Severity (CGI-S) [-.26 (-.44, -.08), p = .004], and CGI-Improvement (CGI-I) [-.22 (-.41, -.03), p = .025] scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia (p = .022). Effect sizes at end point were consistent with moderate benefits. CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.

The biological basis of anxiety. An overview.

The DSM-III divides anxiety disorders into two broad categories, Phobic Disorders and Anxiety States. Anxiety states characterised by panic attacks have been separated from generalised anxiety disorders. While this classification may not be generally accepted it is of heuristic value. Delineation of panic disorder as a distinct diagnostic entity has led to renewed efforts to identify a biological cause for the sudden severe somatic and psychological symptoms experienced by these patients. A review of evidence for the involvement of the major neurotransmitter systems is presented. Systematic investigations in DSM-III defined groups of patients are only beginning to be reported. It is difficult as yet to draw any definite conclusions, but some tentative evidence for abnormalities of the noradrenergic system and the GABA-benzodiazepine chloride ionophore receptor complex are emerging. The reliable induction of panic attacks by chemical agents provides the promise of a greater understanding of the possible biological mechanisms involved in this anxiety disorder.

Definition and differential diagnosis of treatment-resistant depression

There are no agreed criteria for treatment-resistant depression, but the failure to respond adequately to two successive courses of monotherapy with pharmacologically different antidepressants, given in an adequate dose for sufficient time is one pragmatic definition. Inherent within this definition are notions of what constitutes an adequate dose of drug, the length of treatment and pharmacological specificity of treatments. When these factors are accounted for, treatment resistance may be encountered in 15–20% of patients. In attempting to treat such patients a number of pharmacological strategies have been adopted and some are briefly reviewed. Psychosurgery may have a role to play in cases of absolute treatment resistance.

Relationship between antidepressant response and plasma concentrations of fluoxetine and norfluoxetine

The relationship between plasma concentration, clinical outcome and side-effects was examined in 23 patients with major depressive disorder (DSM-III-R) treated with fluoxetine. All patients received a fixed dose of 20 mg for 6 weeks. Good response was observed in 57% of patients, while 30% of patients had moderate responses after 6 weeks of treatment. Fluoxetine and norfluoxetine plasma concentrations were not significantly influenced by age and sex. At 6 weeks, plasma fluoxetine concentrations were not significantly different between responders and non-responders to treatment (82.2 ± 59.6 μg/I vs. 84.7 ± 6.7 μg/I) or those with or without side-effects (74.6 ± 28.7 μg/I vs. 87.0 ± 66.6 μg/I). Similarly, norfluoxetine concentrations were not significantly different for responders and non-responders (65.5 ± 28.9 μg/I vs. 66.5 ± 26.2 μg/I) or those with or without side-effects (66.6 ± 14.4 μg/I vs. 61.5 ± 33.6 μg/l). Plasma concentrations and clinical outcome were not related in a simple manner. Further studies are needed to evaluate the role of monitoring plasma fluoxetine/norfluoxetine concentrations as a routine procedure.

Suicide following acute traumatic spinal cord injury

The rate of suicide following spinal cord injury has not been extensively studied but appears to be greater than in the general population. Six patients who died by suicide, from a total of 342 patients who were treated for acute spinal cord injury over a 5 year period are described. Clinical features shared by this group of patients included being male; having schizoid, depressive or narcissistic personality traits; alcohol or drug abuse; family or significant others favouring death as a preferred option; and the development of significant depression.

Isoniazid and antidepressants : is there cause for concern ?

The antituberculous drug isoniazid has weak monoamine oxidase inhibiting properties. Drug and dietary restrictions generally applied to the use of monoamine oxidase inhibitors (MAOI) have not been routinely recommended with its use. Here we report three cases in which antidepressant drugs and isoniazid were co-administered. In two, adverse events, possibly due to an interaction between the drugs prescribed are described. We suggest that the combination of isoniazid and antidepressants be used with caution until further data are accumulated.

Continuing care of the spinal cord injured

The functions of a comprehensive Spinal Cord Unit do not cease with the discharge of the patient from in-patient treatment after rehabilitation; they extend to aftercare, both in medical follow-up and prevention and treatment of complications, and in ongoing support and education of the patient and his family.An effective aftercare service must offer a life-long commitment to patients, and the aftercare team must include members of the disciplines which were involved in the initial rehabilitation, and also often others. Although demanding of time, resources and money, good aftercare is cost-effective in terms of savings in the cost of out-patient treatment and of re-admissions to hospital for the treatment of complications, and in maintaining many patients in the community, often as contributing members of society.

The psychosocial approach to rehabilitation of the spinal cord injured patient.

The development of a liaison psychiatry service to the Austin Hospital Spinal Injuries Unit highlighted the need for a psychosocial approach to patients rehabilitation. Increasingly we recognised that psychological factors influenced the course of the patients acute illness and rehabilitation; this led to the formation of a psychosocial group under the leadership of the liaison psychiatrist. Membership of this group includes the liaison psychiatrist, psychiatry registrar, clinical psychologist, social workers, visiting nurse, chaplains and the rehabilitation registrar.The psychosocial approach advocates the consideration of psychosocial management in all aspects of patient care. In this paper we describe the structure and function of the psychosocial team in the management of patients in the Spinal Injuries Unit at the Austin Hospital.

Neuroendocrine responses to single doses of buspirone in obsessive-compulsive disorder.

Prolactin and cortisol responses to buspirone, a partial serotonin agonist with effects on the 5-HT 1A, receptor, were measured in 16 patients with DSM-III-R obsessive-compulsive disorder (OCD) and 16 normal controls. No consistent differences were observed between patients and controls with respect to the hormone responses measured. The results suggest that dysfunction of the 5-HT 1A receptor is not present in OCD patients. The limitations of buspirone as a specific agonist challenge of the 5-HT 1A receptor are discussed. Although data from other studies generally support a serotonin dysfunction in OCD, the question of which specific subtype(s) of receptor remains unanswered.

Encephalitis, Catatonia and Schizophreniform Illness

Psychiatric as well as neurological and medical illnesses can give rise to signs of catatonia. DSM 111 (A.P.A., 1980) defines catatonia as a type of schizophrenia in which the essential feature is marked psychomotor disturbance, which may involve stupor, negativism, rigidity, excitement or postur ing. Associated features include stereotypes, mannerisms and waxy flexibility. Mutism is particularly common. The syndrome of acute catatonic delirium associated with fever was described over 100 years ago. It was usually associated with a fatal outcome. Post-mortem examination often failed to reveal the cause of death. English writers called these states ‘acute lethal catatonia’ (Fisher and Greiner, 1960). Symptomatically these syndromes may show catatonic features from the beginning, or they may appear in the course of the psychosis sometimes preceded by delirium. The aetiology of these acute psychoses still remains obscure. Stauder (1934) studied 27 cases and concluded that they belonged to the ‘schizophrenic psychoses’. A study of 55 patients with an acute onset catatonicdelirium state (Laskowska et ul., 1965) showed a high mortality, 20 of the total of 55 (36.4%) dying. Thirty-two patients were followed up over a period from 2-12 years. In 27 cases (84.4%) chronic schizophrenia became apparent, and the remaining five were symptom free. No cases showed evidence of organic dementia. The authors suggested that the psychoses be classified with the group of schizophrenias. I t has long been known that cases of encephalitis may present with symptoms of psychiatric disturbance. Most of the patients show clouding of consciousness and positive neurological findings, so the difficulty in differentiating them from cases of acute functional psychoses is diminished. Psychotic presentations of encephalitis lethargica other than delirium are considered to be rare. In those patients who presented with an acute psychiatric disturbance as the initial feature, mistakes in diagnosis frequently occurred until neurological signs declared themselves. Among these were cases of catatonia (Lishman, 1978). During the epidemic of encephalitis lethargica in England earlier this century, many patients were admitted to mental hospitals with non-specific states of confusion associated with delusions and hallucinations. In later years these patients developed the chronic sequelae of encephalitis lethargica such as parkinsonism, change of personality and mental defect (Lancet, 1966). Argument centred on whether these cases were missed because neurological signs were mild and fleeting, or whether the disease could present in a psychotic form without localising neurological manifest at ions. More recently, Penn et a/. (1972) described a man who seemed to have paranoid schizophrenia and who developed catatonic features over several days. He became hyperthermic and died after nine days, despite electro-convulsive therapy and medical support. A post-mortem examination showed microscopic changes in the central nervous system consistent with viral encephalitis. Several other cases of encephalitis presenting as catatonic illness have been described (Raskin and Frank, 1974). in some, the patient has later shown features of a ‘chronic schizophrenic defect state’ (Mirsa and Hay, 1971).