Karl Burgoyne

Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: results of the BRITE-MD study.

Patients with Major Depressive Disorder (MDD) may not respond to antidepressants for 8 weeks or longer. A biomarker that predicted treatment effectiveness after only 1 week could be clinically useful. We examined a frontal quantitative electroencephalographic (QEEG) biomarker, the Antidepressant Treatment Response (ATR) index, as a predictor of response to escitalopram, and compared ATR with other putative predictors. Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study. After 1 week of treatment with escitalopram, 10 mg, a second QEEG was performed, and the ATR was calculated. Subjects then were randomly assigned to continue with escitalopram, 10 mg, or change to alternative treatments. Seventy-three evaluable subjects received escitalopram for a total of 49days. Response and remission rates were 52.1% and 38.4%, respectively. The ATR predicted both response and remission with 74% accuracy. Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors. Responders had larger decreases in Hamilton Depression Rating Scale (Ham-D(17)) scores at day 7 (P=0.005), but remitters did not. Clinician prediction based upon global impression of improvement at day 7 did not predict outcome. Logistic regression showed that the ATR and early Ham-D(17) changes were additive predictors of response, but the ATR was the only significant predictor of remission. Future studies should replicate these results prior to clinical use.

Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder

We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications.

A typical Antipsychotic Induced Weight Gain: Pathophysiology and Management

There is compelling evidence that patients with schizophrenia are prone to gain weight. In addition, atypical antipsychotic (AAP) drugs also induce weight gain. All antipsychotic drugs produce weight gain but the potential varies. Many studies overwhelmingly confirm that AAP drugs produce substantially more weight gain in comparison to conventional antipsychotic drugs. Clozapine and olanzapine have the most weight inducing potential. Even ziprasidone, which is considered to be weight neutral, and aripiprazole a dopamine modulator produce weight gain in some. The pathophysiology of weight gain is complicated. Many neurohormones, neuropeptides, gut hormones, as well as adipose tissue and hair root derived hormones interact with environmental factors to produce weight gain. Management of weight gain is a difficult problem. Basic to treatment is an understanding of the etiology. Drug induced obesity provides a unique opportunity to psychiatrists to understand this clinically important problem. In the absence ...

Atypical Antipsychotic Drug Use and Diabetes

Recently, there has been increased concern about the occurrence of diabetes associated with the use of atypical antipsychotic (AAP) drugs. The relationship between diabetes, schizophrenia, and antipsychotic drugs is complex and intriguing, as untreated patients with schizophrenia are known to suffer from diabetes more often than the general population. Thirty individual case reports of clozapine-, 26 cases of olanzapine- and a few others of seroquel- and risperidone-associated diabetes mellitus, hyperglycemia and diabetic ketoacidosis were found by a Medline search. The case reports do not provide the incidence of diabetes in patients treated with AAP drugs, but they suggest that AAP drugs may cause hyperglycemia. Further research is needed to identify the cause of the susceptibility of the schizophrenic population, and to elucidate the mechanisms by which the antipsychotic drugs either cause diabetes or precipitate its onset. Which antipsychotic drugs have a higher and which have a lower potential to induce diabetes is not conclusively answered at present. However, the findings that 50% of the patients completely improve upon drug discontinuation, and that hyperglycemia promptly recurs upon reinstitution of the incriminated drug indicate that this side effect is reversible and is drug related. African Americans are particularly susceptible to AAP drug-induced diabetes. Until the new research data become available, AAP drug treatment of schizophrenic patients aims at prevention, institution of vigilant screening procedures, and management of hyperglycemia.

Tardive dyskinesia and ethnicity : Review of the literature

Tardive dyskinesia (TD) is a side effect of long-term neuroleptic administration. The wide variation of 2 to 51% in its reported prevalence can be attributed to the varied definitions of TD, the use of different methods of assessment, and the lack of control of independent variables. Why only certain patients develop this side effect is an intriguing question. The occurrence of TD in family members and in those persons with a family history of Parkinsons disease (PD) is suggestive of genetic vulnerability. Further support for a genetic predisposition comes from the fact that only certain strains of monkeys, such as the Cebus apella strain, have a higher propensity to develop TD than others, such as the Macaca sepciosa strain. If genetic factors play a significant role in the development of TD, then, genetically diverse ethnic groups may have a different propensity for the development of TD. One method of evaluating such a possibility is to compare its prevalence in different countries. The current literature on ethnic differences in the prevalence rates of TD is reviewed. This area of study needs further rigorous investigation.

Quantitative electroencephalogram Biomarkers for predicting likelihood and speed of achieving sustained remission in Major Depression: A report from the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) trial

OBJECTIVE Clinical trials in major depressive disorder (MDD) commonly assess remission at a single endpoint. Complementary, clinically relevant metrics include the likelihood and speed of achieving sustained remission. A neurophysiologic measure, the Antidepressant Treatment Response (ATR) index, previously predicted 8-week outcomes of pharmacotherapy. We retrospectively examined data from the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) trial to evaluate this biomarkers properties in predicting sustained remission and time to achieve sustained remission. METHOD In the BRITE-MD trial, 67 adults with DSM-IV MDD received escitalopram continuously for 13 weeks. The 17-item Hamilton Depression Rating Scale (HDRS17) was used to define sustained remission as achieving remission (HDRS17 score ≤ 7) at a series of consecutive assessments, including week 13. The onset of sustained remission was defined as the earliest time from which all subsequent HDRS17 assessments were ≤ 7. The ATR was evaluated by using frontal quantitative electroencephalogram recordings at baseline and week 1. Subjects were stratified based on ATR status (ie, ATR+/ATR-). Kaplan-Meier survival analysis evaluated group differences in time to sustained remission. Higher ATR was hypothesized to predict sustained remission and time to sustained remission. Subjects participated between January 2006 and July 2007. RESULTS Of 67 subjects, 36 achieved remission by week 13, and ATR predicted this single endpoint in receiver operating characteristic analyses (P = .016; sensitivity, 52.8%; positive predictive value, 76.0%). Remitters had a higher mean (SD) ATR value than those who did not remit (57.9 [10.0] vs 51.9 [8.7], P = .012). Sixteen of the 31 individuals with sustained remission had ATR+ status, while 28 of the 36 who were not sustained remitters had ATR- status (P = .012). The mean time to reach sustained remission was significantly shorter among ATR+ subjects than ATR- individuals (38 vs 53 days, P = .038). CONCLUSIONS The ATR index predicted remission at 13 weeks as well as the speed of achieving sustained remission with antidepressant monotherapy. This finding suggests that the ATR biomarker may predict stable longer-term outcomes. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00289523.

Hepatic disease and psychiatric illness: relationships and treatment.

A relationship between hepatic diseases and psychiatric symptoms has long been speculated. While liver detoxication makes the exogenous substances harmless for the body, there are occasions where the liver may convert a harmless substance into a more toxic substance. With such an important role, the liver protects all the organs of the body. When liver is malfunctioning, toxic metabolites injurious to the brain may be produced. As the brain receives a high blood supply, a large amount of metabolites reach this organ. Hence, the metabolic function of the liver keeps a delicate reciprocal relationship between the two organs. In addition, a number of psychiatric medications affect liver functions. Another perplexing clinical problem is the difficulty in treating psychiatric symptoms in patients with liver disease. For example, benzodiazepines which do not affect the liver function in physically healthy psychiatric patients, may induce hepatic coma in patients with liver disease. Benzodiazepine antagonists produce dramatic and temporary improvement in patients with hepatic coma. Clinically, many psychoactive drugs produce hepatic complications. The very same drugs which produce hepatic side effects are required for the treatment of psychiatric symptoms in patients with hepatic disorders. To appropriately handle these situations, a thorough knowledge of the side effects of these drugs is necessary.

Weight gain associated with atypical antipsychotic drugs: mechanisms and management

Being overweight or obese are medical conditions that are very difficult to treat. There is compelling evidence that obesity is commonly seen in patients with schizophrenia. Recently, a number of publications have focused on the ability of atypical antipsychotic drugs to induce obesity. All antipsychotic drugs produce weight gain, but their potential varies. Many studies overwhelmingly confirm that atypical antipsychotic drugs produce substantially more weight gain in comparison with typical antipsychotic drugs. Clozapine and olanzapine have the most weight-inducing potential. Even ziprasidone, which is considered to be weight neutral, produces weight gain in some patients. The pathophysiology of weight gain is complicated. Many neurohormones, neuropeptides and intestinal hormones, as well as adipose tissue and hair root-derived hormones, interact with environmental factors to produce weight gain. The basis of weight-gain treatment is an understanding of the etiology. Drug-induced obesity provides a unique opportunity to psychiatrists to understand this true psychosomatic problem. In the absence of this knowledge, prevention is the best hope. Education, diet control and simple behavioral measures may prevent excessive weight gain. In those with weight gain, treatment can be attempted with pharmacotherapy.

Pharmacotherapy for refractory schizophrenia patients

Most schizophrenic patients experience morbidity over the course of their illness, as the illness runs a chronic course and full remissions are infrequent. Therefore, defining treatment resistance among schizophrenia is problematic. Not all patients respond to antipsychotic medication treatment and an estimated 30–50% are considered resistant to treatment. Treatment resistance normally occurs along a continuum and most patients manifest varying degrees of resistance to antipsychotic medications. Essock and colleagues discovered that more than 60% of the patients in state hospitals met the criteria for clozapine therapy and, therefore, they may qualify for treatment resistance [1].

Presence of Antibrain Antibodies in Obsessive-Compulsive Disorder Secondary to Pineal Gland Germinoma: A Case Report

Received March 26, 2013; revised April 30, 2014; accepted May 1, 2014. From Department of Psychiatry, Harbor-UCLA Medical Center, David-Geffen School of Medicine, University of California, Los Angeles, CA. Send correspondence and reprint requests to Weiguo Zhu, Department of Psychiatry, Harbor-UCLAMedical Center, 1000W Carson Street, Torrance, Los Angeles, CA 90509; e-mail: wzhumd@ ucla.edu Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine. Introduction