Treatment-resistant schizophrenia: How far have we traveled?

Treatment-resistant schizophrenia is a lack of adequate response to antipsychotic medications resulting in incomplete functional and social recovery from the illness. Different definitions have been proposed for clinical practice and research work. Antipsychotics that are used in the management of schizophrenia mainly act on multiple dopaminergic pathways which are implicated in the development of symptoms of schizophrenia. Newer antipsychotics also are implicated to affect the serotonergic pathways. Clozapine is the only evidence-based treatment available for the management of treatment-resistant cases. Neurobiologically, there is a considerable overlap between treatment-resistant and treatment-responsive cases. The factors that are implicated in the evolution of treatment resistance are still not conclusive. These make the management of such patients a challenge. However, certain peculiarities of treatment-resistant schizophrenia have been identified which can guide us in the early identification and precise treatment of the treatment-resistant cases.

Suicidal ideation in schizophrenia: A cross-sectional study in a tertiary mental hospital in North-East India.

INTRODUCTION: Suicide is a leading cause of mortality in schizophrenia. The study attempts to find an association of suicidal ideation, a less studied entity than suicide attempt, with various sociodemographic and clinical profiles in patients with schizophrenia. MATERIALS AND METHODS: It is a cross-sectional study involving 140 patients diagnosed as schizophrenia. Sociodemographic and clinical profiles were collected using a semi-structured proforma. Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, InterSePT Scale for Suicidal Thinking, and Drug Attitude Inventory-10 were applied to assess psychopathology, depressive symptoms, suicidal ideas, and attitude toward psychotropics, respectively. The analysis was done using appropriate statistics. RESULTS: Majority of the study sample were Hindus, male, unmarried, literate, unemployed, and belonging from lower socioeconomic class. About 25.7% attempted suicide earlier and 29.3% currently have suicidal ideation. A previous suicide attempt, family history of psychiatric illness and that of suicide and comorbid substance use, significantly predicted (p < 0.05) a current suicidal ideation. Ideation has also been found to be significantly correlated to comorbid depression and the positive, negative, emotional, and excitement domains of schizophrenic psychopathology. CONCLUSION: The current study shows suicidal ideations in schizophrenia patients to be significantly related to schizophrenic psychopathology and comorbid depression, thus calling for a holistic management in preventing a fatal outcome.

Aggression as an independent entity even in psychosis - The role of cortisol.

Aggression is a common entity in psychiatric disorders, particularly psychotic disorders. Glucocorticoid hypofunction has been linked to abnormal forms of aggressive behavior in various studies in a 'possibly causal' role. We hypothesise that aggression, even among those having psychosis is associated with glucocorticoid alterations similar to those who are aggressive but not psychotic. To our knowledge, this is the first study attempting to look at the cortisol functioning in relation to both aggression and psychosis. The present study included 80 participants divided into four groups depending upon presence or absence of aggression and psychosis. Morning cortisol, afternoon cortisol and their variability were measured using ELISA. The groups were compared on measures of aggression, psychosis, morning cortisol, afternoon cortisol and their variability using standard statistical instruments. The present study found lower levels of morning cortisol, afternoon cortisol and cortisol variability among the aggressive group (vs. non aggressive group) and among the diseased group (vs. non diseased group). The differences were most marked for cortisol variability which was related to both aggression and psychosis independently. There were statistically significant correlation between cortisol variability and aggression, which was retained even after controlling for psychosis. There was no significant correlation of cortisol variability with psychosis severity (after controlling for aggression score) or with age, gender or duration of psychosis. We conclude that aggression, even among patients with psychosis, is an independent entity characterized by lower levels of morning cortisol and cortisol variability. The etio-pathology may lie in some altered neuro-immune parameters executed by cortisol and psychosis as trigger.

Sociodemographic Correlates of Unipolar and Bipolar Depression in North-East India: A Cross-sectional Study.

INTRODUCTION: Early diagnosis and management of depression is important for better therapeutic outcome. Strategies for distinguishing between unipolar and bipolar depression are yet to be defined, resulting improper management. This study aims at comparing the socio-demographic and other variables between patients with unipolar and bipolar depression, along with assessment of severity of depression. MATERIALS AND METHODS: This cross sectional study was conducted in a tertiary care psychiatry hospital in North-East India. The study included total of 330 subjects selected through purposive sampling technique from outpatient department after obtaining due informed consent. Mini-International Neuropsychiatric Interview (M.I.N.I.) version 6.0 and Beck Depression Inventory (BDI) were applied. Statistical Package for Social Sciences (SPSS) version 16.0 was applied for analysis. RESULTS: Bipolar group had onset of illness at significantly younger age with more chronicity (32.85 ± 11.084). Mean BDI score was significantly higher in the unipolar depressive group. CONCLUSION: Careful approach in eliciting symptom severity and associated socio demographic profiles in depressed patients may be helpful in early diagnosis of bipolar depression.

Aggression as an independent entity even in psychosis- the role of inflammatory cytokines.

BACKGROUND: Aggression is very common in psychosis (prevalence ranging from 34% to 70%) and is often the main or first symptom for which the patient receives medical attention. Studies have associated alteration in cytokine profiles among healthy persons with aggressive traits. We hypothesise that even among those with psychosis, aggression is an independent entity, irrespective of psychotic state and is associated with cytokine alterations. To our knowledge, this is the first study attempting to look at the inflammatory cytokines in aggressive psychotic patients. METHODS: Study included 80 participants divided into four groups viz. aggressive diseased, non aggressive diseased, aggressive non diseased and non aggressive non diseased depending upon presence or absence of aggression and psychosis. Interferon gamma(IFN-G), Interleukin 10(IL10) plasma concentrations and their ratio were measured using ELISA based assay kits read at absorbance of 450 nm wavelength using Double beam spectrophotometer. The four groups were compared on measures of aggression, psychosis, Interferon Gamma levels, Interleukin 10 levels, Proinflammatory: Antiinflammatory cytokine ratio using standard statistical instruments. RESULTS: In patients with psychosis, the cytokines IFN-G and IL10 were significantly lower compared to those without. The cytokines IFN-G and IL10 are both significantly associated both with aggression and psychosis. IL10, but not IFN-G is associated with aggression in absence of psychosis. The proinflammatory: antiinflammatory cytokine ratio, is more significantly associated with aggression, irrespective of psychosis. In fact, there is no significant relationship between the above ratio and psychosis. Strong correlation exists between the proinflammatory: antiinflammatory cytokine ratio and aggression scores, even after controlling for severity of psychosis. CONCLUSIONS: It may be concluded from this study that in spite of a high prevalence of aggression in patients of psychosis, it is more likely to be an independent entity associated with individual cytokine changes and increased proinflammatory: antiinflammatory cytokine ratio as its hallmark.

Aripiprazole-induced skin rash.

Adverse skin reactions are an important type of adverse drug reactions which have been reported with a wide variety of psychotropics including both typical and atypical antipsychotics. Like typical antipsychotics, atypical antipsychotics such as olanzapine, risperidone, and paliperidone have been documented to cause skin reactions. Reports of aripiprazole-induced skin reactions are sparse. We report a case of skin rash that developed after starting aripiprazole in a male patient suffering from schizophrenia and which remitted after the drug was stopped.

IPS multicentric study: Functional somatic symptoms in depression.

BACKGROUND: As a pilot project, Indian Psychiatric Society conducted the first multicentric study involving diverse settings from teaching institutions in public and private sectors and even privately run psychiatric clinics. AIM OF THE STUDY: To study the typology of functional somatic complaints (FSC) in patients with first episode depression. MATERIALS AND METHODS: A total of 741 patients from 16 centers across the country participated in the study. They were assessed on Bradford Somatic Symptom inventory for FSC, Beck Depression Inventory for severity of depression, and Comprehensive Psychopathological Rating Scale- anxiety index (CPRS-AI) for anxiety symptoms. RESULTS: The mean age of the study sample was 38.23 years (SD-11.52). There was equal gender distribution (male - 49.8% vs. females 50.2%). Majority of the patients were married (74.5%), Hindus (57%), and from nuclear family (68.2%). A little over half of the patients were from urban background (52.9%). The mean duration of illness at the time of assessment was 25.55 months. Most of the patients (77%) had more than 10 FSCs, with 39.7% having more than 20 FSCs as assessed on Bradford Somatic Inventory. The more common FSC as assessed on Bradford Somatic Inventory were lack of energy (weakness) much of the time (76.2%), severe headache (74%) and feeling tired when not working (71%), pain in legs (64%), aware of palpitations (59.5%), head feeling heavy (59.4%), aches and pains all over the body (55.5%), mouth or throat getting dry (55.2%), pain or tension in neck and shoulder (54%), head feeling hot or burning (54%), and darkness or mist in front of the eyes (49.1%). The prevalence and typology of FSCs is to a certain extent influenced by the sociodemographic variables and severity of depression. CONCLUSION: Functional somatic symptoms are highly prevalent in Indian depressed patients and hence deserve more attention while diagnosing depression in Indian setting.

IPS multicentric study: Antidepressant prescription patterns.

BACKGROUND: There are very few studies from India which have evaluated the prescription pattern for antidepressants by psychiatrists for treatment of depression. AIM: To study the psychotropic prescription patterns of patients with first episode depression from diverse settings including teaching institutions in public and private sectors and even privately run psychiatric clinics. MATERIALS AND METHODS: Prescription data of 706 patients with first episode depression, who participated in the IPS multicentric study, were evaluated. RESULTS: Escitalopram was the most commonly prescribed antidepressant, comprising 40% of the total prescriptions. This was followed by sertraline (17.6%) and fluoxetine (16.3%). In total, selective serotonin reuptake inhibitors (SSRIs) formed 79.2% of all the prescriptions. Tricyclic antidepressants formed a small part (15.15%) of total prescriptions, with imipramine being the most commonly used tricyclic antidepressant. Serotonin-norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine and duloxetine) were prescribed to 11.3% of patients with equal share of venlafaxine and duloxetine. About one-sixth (N=104; 14.7%) of the patients were prescribed more than one antidepressant. Nearly three-fourth of the patients (N=523; 74.1%) were prescribed a benzodiazepine, with clonazepam being the most preferred agent, prescribed to nearly half of the participants (49%) and formed nearly two-third of the total benzodiazepine prescriptions (346 out of 523). CONCLUSION: Escitalopram is the most commonly prescribed antidepressant and SSRIs are the most commonly prescribed class of antidepressants. Poly pharmacy in the form of concomitant use of two antidepressants is practiced infrequently. However, benzodiazepines are used quite frequently as the co-prescription.

Disability in a Group of Long-stay Patients with Schizophrenia: Experience from a Mental Hospital.

BACKGROUND: Recovery from schizophrenia is a complex concept. Remission of symptoms of psychotic illnesses is not necessarily linked to better functioning. Among various causes of disability, mental illnesses account for 12.3% of the global burden of diseases. Long-term hospitalization has been recognized as counterproductive and a contributory factor of disability associated with schizophrenia. Under various circumstances, many persons with mental illness are brought to mental hospitals but the measures taken for their rehabilitation and follow-up care is insufficient. AIM: In the present study we tried to find out the level of psychopathology and the associated disability in a group of patients with schizophrenia who have been staying in a mental health institution for more than 5 years due to lack of proper caregivers in the society or in their home. MATERIALS AND METHODS: The study is conducted in a mental hospital of northeast India. Of the 40 patients staying for more than 5 years in the hospital, 28 fulfilled the criteria for inclusion. The Brief Psychiatric Rating Scale and World Health Organization Disability Assessment Schedule II (WHO DASII) were used for those patients. Analytical statistical methods were used subsequently. RESULTS: Male patients were significantly older and had prolonged duration of stay. But the level of psychopathology did not differ significantly between male and female patients. Under WHODASII, understanding and communication problems are more prominent in both the groups. Of late, there are very few cases that required prolonged stay in the hospital. Many patients are fairly functional and are considered suitable for care outside hospital premises. CONCLUSION: Prolonged hospital stay is associated with more disability. Shorter hospital stays with proper family support is an ideal way to counteract this issue. However, due to the inadequate mandate in the Mental Health Act (MHA) 1987 and lack of other supportive facilities, patientsoften tend to languish in the hospital for longer duration, causing harm to the patients and draining scarce state resources. It is therefore necessary to revisit the MHA 1987 and provide adequate rehabilitative measures for the needy patients.