Current Psychiatry Reviews - Volume 9, Issue 2, 2013

Catatonic schizophrenia has been an integral part of all psychiatric classifications for over a century. However, based on the recommendation of a panel of experts, catatonic schizophrenia as an independent diagnostic entity will probably be removed form DSM-V. This review paper summarizes the history, psychopathology and clinical features of catatonic schizophrenia and argues that a cluster of loosely defined, simple and complex motor phenomena is an inherent aspect of the symptomatology of schizophrenia. In the authors’ opinion, the motor aspects of descriptive psychopathology in general, and in schizophrenia in particular have not received ample attention in modern research and clinical practice. As a consequence, there is a dearth of scientific data on the epidemiology, psychopathology, genetics, treatment response and biological markers that would have justified and cemented its place in modern classifications.

Catatonia was described by Kahlbaum in 1874 as a putative disease entity and was subsumed under dementia praecox by Kraepelin in 1896. Although a number of studies attested to the occurrence of catatonia in several other clinical conditions (major psychiatric disorders and organic brain disturbances), its place in modern classifications is still debated. While the traditional clinical stereotype have equated catatonia with schizophrenic psychosis, modern studies in the last three decades observed catatonia in approximately 10% of acute psychiatric admissions, most frequently in association with mood disorders. Catatonic signs (such as mutism, stereotypy, posturing, catalepsy, automatic obedience, negativism, echolalia/echopraxia, or stupor) occur in 13-31% of patients with affective disorders. Recent studies confirmed that catatonic signs are present in 28-66% in different phases of Bipolar Affective Disorder and Schizoaffective Disorder, bipolar subtype. In these cases, manic symptoms are more prominent and mixed states are more frequent. Catatonic signs occur most frequently (approx 61%) in mixed affective states and 46% of these patients require admission to an emergency psychiatric unit. Catatonic symptoms are found in 31-62% of patients with mania. Presence of catatonia is associated with more severe manic phases. Depression is associated with catatonic signs in 20-53%. Catatonia usually indicates the severity of depressive state but its presence is also a predictor of favorable treatment response. The prompt recognition of catatonic signs is important since catatonia in patients with affective disorders responds rapidly to benzodiazepines or electroconvulsive therapy which could be a lifesaving intervention. Appropriate prophylactic treatment of affective disorders is of crucial importance in this respect.

While much has been written about catatonia, there are only a few scholarly reviews focused on catatonia due to a general medical condition, also referred to as organic catatonia. There has been a long list of causative conditions that account for the development of organic catatonia which are informative but not clinically helpful. We performed a literature search using the term ‘catatonia’ covering the last ten years. We found 31 titles of catatonia due to drugs and 76 titles of catatonia due to a general medical condition. Of these, 9 were catatonia due to NMDA antibody associated encephalitis. In order to update this body of knowledge, we have revisited the differential diagnosis of catatonia and attempted to delineate catatonia due to a general medical condition from phenomenologically similar but etiologically disparate conditions. We also focused on catatonia due to systemic lupus erythematosis. We also present a case of catatonia due to hydrocephalus to illustrate treatment issues. In spite of the pharmacologic treatment for catatonia, this patient has not improved. We hope that this review and discussion will aid in the identification and treatment of catatonia due to a general medical condition. Medical causes must be addressed to ensure the best outcome.

Malignant catatonia (MC) represents a life-threatening neuropsychiatric disorder that was widely reported long before the introduction of antipsychotic drugs. A review of the world literature on MC indicates that although the prevalence of the condition may have declined since the pre-antipsychotic drug era, it continues to occur and represents a syndrome rather than a specific disease. Although most often the outgrowth of a psychiatric disorder, MC may develop in association with diverse neurologic and medical conditions. From this perspective, neuroleptic malignant syndrome (NMS) may be viewed as a drug-related form of this same MC syndrome. Our review also supports the proposed conceptualization of catatonia as a continuum, with milder forms at one end (termed simple or nonmalignant catatonia) and more severe forms involving hyperthermia and autonomic dysfunction (termed malignant catatonia) at the other end. In addition, findings from our review suggest that simple catatonia, MC and NMS share a common pathophysiology involving reduced dopaminergic functioning in the basal ganglia-thalamocortical circuits, consistent with their identity as variants of the larger unitary catatonic syndrome. Electroconvulsive therapy appears to represent the preferred treatment for MC. Antipsychotic drugs should be withheld whenever MC is suspected.

There has been renewed interest in the demarcation of pediatric catatonia from other pediatric conditions including autism. An update on symptoms, prevalence, evaluation, treatment, risk factors, and experimental models of pediatric catatonia is presented. Recent prevalence rates of pediatric catatonia vary widely across studies, suggesting that catatonia may not be rare in younger patients. Symptoms and diagnostic criteria for pediatric catatonia are the same as in adults. Studies and clinical experience support benzodiazepines and electroconvulsive therapy, including maintenance electroconvulsive therapy, as treatment options. Sometimes catatonia develops after severe psychological trauma. Historical and contemporary clinical and experimental catatonia models are available for future research, focusing on motor circuitry dysfunction, abnormal neurotransmitters, epileptic discharges, genetics, neuroendocrine and immune abnormalities, fear reactions akin to the animal defense strategy of tonic immobility, and developmental risk factors. There have been advances in demarcating pediatric catatonia in a wide variety of patients as a treatable condition that requires prompt identificiation. A model of developmental impairment complements clinical and experimental catatonia models.

Catatonia is a severe neuropsychiatric syndrome comprising a variety of signs and symptoms ranging from simple motor signs to complex behavioural abnormalities. If recognized and treated early, catatonia usually has an excellent prognosis. Observation and psychiatric interview will not suffice to detect the catatonic syndrome, since the most striking symptoms such as posturing, are present only in a minority of the cases. Therefore, catatonic signs should be elicited during a neuropsychiatric examination. Patients with severe psychiatric conditions, such as bipolar disorder, depression or schizophrenia, should be examined routinely for catatonic signs and symptoms. A number of rating scales, such as the Bush-Francis Catatonia Rating Scale, are available offering the clinician a scheme to aid neuropsychiatric examination. The most robust argument for identifying catatonia as a separate syndrome is that it has a rather specific treatment, either benzodiazepines or electroconvulsive therapy (ECT), irrespective of the underlying etiology. Among the benzodiazepines, lorazepam is the best studied and is currently used as first line treatment for catatonia. ECT in recent clinical practice is usually considered as second line treatment for the syndrome, although in certain conditions, especially in malignant catatonia, its early administration could be lifesaving. A further issue supporting the use of ECT in catatonia is that regardless of the origin of the condition it is effective, while certain antipsychotics or antidepressants can even worsen catatonic phenomena if they go unrecognized.

Objectives: Our understanding of the pathogenesis of schizophrenia is limited. In this regard, there have been a number of reports of altered thiol metabolism in schizophrenia. The aim of this review is to integrate disparate published findings into a more global overview of altered thiol metabolism and the potential role of thiol therapy in schizophrenia. Methods: Publications of thiol measurements in different metabolic compartments in schizophrenic patients (SP) were organized with regard to which component pathway of overall thiol metabolism was involved. This formed the basis of providing an integrated interpretation of current published data. With regard to clinical trials of thiols, there are a number of case reports and studies with small patient numbers. The reliability of these trials is questionable such that we reviewed the one double-blind study evaluating the thiol agent, Nacetylcysteine (NAC) on clinical outcomes in 69 SP. We also reviewed 2 small mechanistic studies in SP evaluating the effects of NAC on EEG synchronization and on mismatch negativity, an electrophysiological index of glutamatergic transmission at NMDA receptors. Results: The data reviewed were consistent with dysfunctional thiol metabolism spanning the methionine-homocysteine cycle, through the trans-sulfuration pathway to GSH synthesis and metabolism. Additionally, several thiol-dependent pathways appear to be affected. Preliminary clinical trials with NAC suggest that thiol replacement strategies may represent a new therapeutic avenue for SP. Larger patient cohorts are required to substantiate these initial findings and will provide an opportunity to monitor the effects of thiol drugs on biomarkers of altered thiol metabolism in SP. Limitations: There are a number of reports of altered thiol metabolism in SP and indications of clinical benefits with the thiol agent NAC, as an adjunct to antipsychotic drugs. However, these are all probe studies with small numbers of patients. The next step is to a more in-depth evaluation of thiol metabolism and larger scale clinical trials of thiol agents. Integrating clinical and biochemical findings will significantly advance our knowledge base in this area. Conclusion: Thiol metabolism is clearly disrupted in SP and thiol replacement strategies are worthy of further clinical evaluation, based on initial pilot studies with NAC in SP.

Background: The relationship between plasma concentrations of psychiatric medications and their efficacy is rarely evaluated or relied upon in clinical practice. While it is generally accepted in clinical settings that patients respond to varying doses of medication, few studies have formally tested whether plasma concentrations of psychiatric medicine predict patients’ responses. We hypothesized that the amount of mifepristone detected in the plasma after dosing for 7 days would correlate with reduction of psychotic symptoms in patients with psychotic depression. This hypothesis was generated from the exploratory analysis phase of an early clinical trial. In that trial, a statistically significant linear correlation was observed between change in psychotic symptoms and mifepristone plasma concentrations observed at day 7. Method: Secondary analyses were conducted using data from three multicenter randomized clinical trials. For each of the three trials, hypothesis testing was conducted to test whether patients assigned to mifepristone whose plasma concentrations were above pre-specified concentration values would exhibit significantly greater reduction in psychotic symptoms than patients assigned to placebo. Results: In all studies, there was a statistically significant linear correlation between plasma concentration and change in psychotic symptoms. In two of the three clinical trials, the response rate of patients with mifepristone plasma concentrations above 1660 ng/ml was significantly greater than the placebo response rate. Results are presented for the three studies separately and for the combined data. Discussion: Although correlations between plasma correlations and clinical response are not often observed in psychiatric medications, there is evidence that trough mifepristone plasma concentrations are associated with clinical improvement. Study identification numbers clinicaltrials.gov: NCT00130676 (Study 07), NCT00146523 (Study 09), NCT00128479 (Study 06).

Comorbidity among people with psychiatric conditions is common and is associated with complicated course, poorer treatment outcomes, higher rates of treatment utilization, and higher risk of mortality. However, research on comorbidity continues to be under-represented in the field. This paper presents the Integrated Framework of Comorbidity to promote and improve research and clinical development in the treatment of comorbidity. The Framework has five domains: I) comorbidity influences, II) comorbid disorders or conditions, III) health care interactions of those with comorbidity, IV) comorbidity outcomes, and V) comorbidity associations. Using the Framework should lead investigators to do the following: 1) examine additional outcomes relevant to their area, 2) consider real-world barriers to the implementation of effective treatments of comorbid conditions, and 3) consider etiological mechanisms carefully when testing the effectiveness of treatments of comorbid conditions. The Framework is meant as a general research and clinical heuristic. Implications of the Framework for research and the development of clinical approaches are also discussed.

People with schizophrenia continue to smoke at higher rates than the general population. Yet, care providers do not routinely aggressively treat this addiction, despite an extensive literature supporting that people with schizophrenia can tolerate cessation attempts. The rationale for not treating smoking addiction will be addressed, and then the intervention literature reviewed. Some clinical issues and areas which need for further study will be discussed.