Ananda K. Pandurangi

Is bipolar disorder still underdiagnosed? Are antidepressants overutilized?

BACKGROUND Previous studies have suggested that bipolar disorder may be underdiagnosed, and that antidepressants may be over-utilized in its treatment. METHODS Consecutively admitted patients (n =48) diagnosed with DSM-IV bipolar disorder, type I, (n = 44) or schizoaffective disorder, bipolar type, (n = 4) were interviewed systematically and their charts were reviewed to confirm diagnosis before admission. They were then treated according to systematic structured interview diagnoses. These data reflect the changes in diagnoses and treatment. RESULTS 40% (19/48) were identified with previously undiagnosed bipolar disorder, all previously diagnosed with unipolar major depressive disorder. A period of 7.5+/-9.8 years elapsed in this group before bipolar diagnosis was made. Antidepressant use was high on admission (38%) and was reduced with acceptable treatment response rates. The adjunctive use of risperidone appeared to be a good treatment alternative. LIMITATIONS While diagnoses were made prospectively, treatment response was assessed retrospectively, and was based on non-randomized, naturalistic therapy. CONCLUSIONS Systematic application of DSM-IV criteria identified previously undiagnosed bipolar disorder in 40% of a referred population of patients with mood disorders, all previously misdiagnosed as unipolar major depressive disorder. Antidepressants appeared overutilized and risperidone was an effective alternative adjunctive therapy agent.

Sustained attention and positive formal thought disorder in schizophrenia

Deficits in sustained attention and formal thought disorder (FTD) are two characteristics of schizophrenia that might be expressions of a common pathology. This study examined whether a measure of enduring (post-treatment, stabilized) deficits in sustained attention, the Continuous Performance Test (CPT) could predict FTD. In addition, a comparison was made of CPT performance between subjects with schizophrenia (n = 41) and healthy controls (n = 28). Results replicated previous findings of significantly poorer performance by individuals with schizophrenia compared to normal controls. Within the schizophrenia group, significant correlations were found between FTD and CPT measures. In order to assess predictability of FTD, a hierarchical multiple regression analysis was used. CPT errors and gender both significantly predicted FTD. The most robust prediction was of residual FTD (post-treatment, stabilized) by CPT commission errors. These results lend support to the proposition that a subsyndrome within schizophrenia exists that is characterized by deficits in sustained attention and positive formal thought disorder. Furthermore, this subsyndrome might be more common in males than females.

Quetiapine and the need for a thorough QT/QTc study

The Food and Drug Administration (FDA) directed AstraZeneca in 2011 to add a warning to the labeling of the atypical antipsychotic agent quetiapine (Seroquel) about quetiapine-induced QTc interval prolongation and the potential for drug-induced torsade de pointes (TdP). This warning was updated the following year. Rather than relying on a thorough QT/QTc (TQT) study, this update was based on postmarketing reports of patients (1) overdosing on quetiapine, (2) having severe hypokalemia, or (3) receiving drugs associated with QTc interval prolongation such as (1) class I-A or class III antiarrhythmics, (2) certain antipsychotics (eg, ziprasidone, chlorpromazine, thioridazine), (3) certain antibiotics (eg, gatifloxacin, moxifloxacin), or (4) any other classes of drugs linked to QTc interval prolongation (eg, pentamidine, L-methadyl acetate, methadone). Interestingly, of the 3095 patients, 2 (0.06%) developed QTc interval prolongation of more than 500 milliseconds in quetiapine premarketing trials. They were older women with dementia. There was no link between quetiapine dose and QTc interval prolongation. Here, we evaluate available information on quetiapine in respect of QTc inteval prolongation and TdP, taking into account both information from preclinical experimental studies and human data. A striking feature of the latter is a lack of information from ‘‘thorough QT’’ (TQT) studies. We argue that TQT data for quetiapine would be invaluable in reaching an integrated assessment of its cardiac risk.

TARDIVE DYSKINESIA IN NON-WESTERN COUNTRIES : A REVIEW

Tardive dyskinesia (TD) is a well-described adverse effect of treatment with neuroleptics. Studies from non-western countries are sparse and those that exist are not well publicized. We analyzed prevalence data on TD, published in English or French, and carried out in countries in Africa and Asia through December 1993. The estimated prevalence of TD among African subjects was 24% and among Asian subjects 17.20%. Both rates are in the middle range when compared with the western prevalence rates of 10–50%. Long-term hospitalization and older age were risk factors associated with TD. Female gender did not emerge as a risk factor. Also, several Asian studies showed that subjects with TD were taking lower doses of neuroleptics than subjects without TD. Prospective and controlled cross-cultural studies of TD are recommended for better understanding of associated risk factors and primary prevention.

A brief analysis of suicide methods and trends in Virginia from 2003 to 2012

Background. The objective is to analyze and compare Virginia suicide data from 2003 to 2012 to US suicide data. Methods. Suicide trends by method, age, gender, and race were obtained from Virginias Office of the Chief Medical Examiners annual reports. Results. Similar to US suicide rates, suicide rates in Virginia increased between 2003 and 2012 from 10.9/100,000 people to 12.9/100,000 people. The most common methods were firearm, asphyxia, and intentional drug overdose, respectively. The increase in asphyxia (r = 0.77, P ≤ 0.01) and decrease in CO poisoning (r = −0.89, P ≤ 0.01) were significant. Unlike national trends, intentional drug overdoses decreased (r = −0.55, P = 0.10). Handgun suicides increased (r = 0.61, P = 0.06) and are the most common method of firearm suicide. Hanging was the most common method of asphyxia. Helium suicides also increased (r = 0.75, P = 0.05). Middle age females and males comprise the largest percentage of suicide. Unlike national data, the increase in middle age male suicides occurred only in the 55–64-year-old age group (r = 0.79, P ≤ 0.01) and decreased in the 35–44-year-old age group (r = −0.60, P = 0.07) and 10–14-year-old age group (r = −0.73, P = 0.02). Suicide in all female age ranges remained stable. Caucasians represent the highest percentage of suicide. Conclusion. There has been a rise in suicide in Virginia and suicide rates and trends have closely resembled the national average albeit some differences. Suicide prevention needs to be enhanced.

Electroconvulsive Therapy in a Candidate for Heart Transplant With an Implantable Cardiovertor Defibrillator and Cardiac Contractility Modulator

BACKGROUND Electroconvulsive therapy (ECT) can be life-saving in treating depression, even for high-risk cardiac patients. A 56-year-old man with type 2 diabetes and dilated cardiomyopathy, using both a defibrillator and an experimental cardiac contractility modulator, had had episodes of severe depression superimposed on dysthymia for 27 years, with a current exacerbation over the past 2 years, and little response to antidepressant treatment. METHOD He received a course of 12 ECTs (6 right-unilateral and 6 left-anterior/right-temporal electrode placements). RESULTS After these, he was judged moderately but not dramatically improved. DISCUSSION Serious adverse events, such as myocardial infarction, lethal arrhythmias, and cardiac rupture are possible in these high-risk patients, especially those with ejection fractions <50%, previous myocardial infarction, or significant arrhythmias. This case illustrates the complex decision-making involved and the need for close interdisciplinary collaboration entailed in preparing a high-risk patient with an implanted device for ECT.

Delayed Onset and Prolonged ECT-Related Delirium

Electroconvulsive therapy (ECT) is effective in the treatment of depression. Delayed post-ECT delirium is rare but can occur in a small subset of patients with risk factors and in most cases resolves with the use of psychotropic medications. We report a unique presentation of a patient who developed a delayed post-ECT delirium with fecal incontinence that commenced 24 hours after the administration of ECT. The condition resolved spontaneously after 48 hours without the use of psychotropic medications.

Bilateral ulnar nerve paralysis: an unreported complication of drug-induced extrapyramidal rigidity

Objective: This case report describes a very unusual consequence of drug-induced extrapyramidal side effects. Clinical picture: The patient developed bilateral ulnar nerve paralysis. Treatment: The treatment consisted of anticholinergic medication and physiotherapy. Outcome: The patient made a complete recovery over a period of 8 months. Conclusions: There is a need to ensure compliance with anticholinergic medication when using depot neuroleptic medication.

Augmentation Therapy With Serial Intravenous Ketamine Over 18 Months in a Patient With Treatment Resistant Depression.

Major depressive disorder is a severe illness that affects 3% to 7% of adults annually in the United States. About 30% of these individuals are refractory to multiple treatment trials. Recent reports have found a significant and almost immediate improvement in depressive symptoms after single or multiple ketamine intravenous infusions (IVIs) in such patients. We present the case of A.B., a patient with treatment-resistant depression (TRD) including to subgenual deep brain stimulation, who went into remission after augmentation with 6 ketamine IVIs (0.5 mg/kg) over a 3-week period. However, she had a reemergence of depressive symptoms 4 months later and received a second series of 3 ketamine IVIs over the course of a week. A.B. again went into remission and maintained this for the next 8 months. At this time, she experienced a reemergence of depressive symptoms and was treated with the third series of ketamine IVIs (3 infusions over the course of a week). Because A.B. has now been in remission for 6 months. A.B. has received a total of 12 ketamine IVIs over the course of 18 months. No significant adverse events have occurred. To our knowledge, this is the first case of long-term ketamine efficacy as augmentation therapy in TRD over the course of 18 months. There is a need for studies examining the long-term management of TRD with IV ketamine. Guidelines for maintenance ketamine IVIs in TRD also need to be developed.

QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment

Background: QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. Objectives: In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. Patients and Methods: ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. Results: The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. Conclusions: The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.