Jayesh Kamath

Management options for established chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a variety of chemotherapeutic agents. Clinicians are cognizant of the negative impact of CIPN on cancer treatment outcomes and patients’ psychosocial functioning and quality of life. In an attempt to alleviate this problem, clinicians and patients try various therapeutic interventions, despite limited evidence to support efficacy of these treatments. The rationale for such use is mostly based on the evidence for the treatment options in non-CIPN peripheral neuropathy syndromes, as this area is more robustly studied than is CIPN treatment. In this manuscript, we examine the existing evidence for both CIPN and non-CIPN treatments and develop a summary of the best available evidence with the aim of developing a practical approach to the treatment of CIPN, based on available literature and clinical practice experience.

Desvenlafaxine succinate for major depressive disorder: a critical review of the evidence

Desvenlafaxine succinate (DVS) is the succinate salt monohydrate of O-desmethylvenlafaxine, an active metabolite of venlafaxine. DVS is a serotonin–norepinephrine reuptake inhibitor (SNRI) like venlafaxine, but exhibits a differential serotonergic and noradrenergic activity profile. A sustained-release form of DVS is approved by the US FDA for the treatment of adult major depressive disorder (MDD). DVS has shown efficacy for the treatment of MDD in clinical trials with doses ranging from 50 to 400 mg/day. The 50–100 mg/day dose range is therapeutic, with lack of additional benefit shown at higher dosages and a significantly higher risk of side effects, especially at the 400 mg/day dosing. Advantages of DVS over other sSNRIs include its simple metabolism, lower risk of drug–drug interactions and lack of need for extensive titration to achieve therapeutic efficacy. Limitations with the use of DVS include its moderate efficacy in the treatment of MDD, a safety–tolerability profile similar to that of other SNRIs and the possibility of transient discontinuation symptoms with cessation of DVS treatment. DVS is a useful addition to the options available for the treatment of MDD in light of the limited efficacy of currently available antidepressants.

New approaches for the treatment of sleep disorders.

Epidemiological studies have established that sleep disorders are common and often untreated. Besides having a negative impact on overall health, these conditions can significantly disrupt normal daily functions. While a number of drugs are employed in the treatment of sleep disorders, safety, tolerability, and variable efficacy limit their utility. Clinical developments in the area have been facilitated especially by advances in neurobiology and neuropharmacology. In this regard, a wide array of neuroactive substances has been found to be responsible for regulating sleep and wakefulness. Advances in the understanding of neurotransmitter and hormone receptor mechanisms and classifications have led to new opportunities for developing novel therapeutics for treating sleep disorders. Provided in this report is an overview of some of the more prevalent sleep disorders, including narcolepsy, insomnia, obstructive sleep apnea syndrome, and restless legs syndrome, with a summary and critique of medications used to treat these conditions. For each disorder, information is provided on recent approaches taken to develop novel therapeutics based on laboratory findings relating to the underlying biological abnormalities associated with the condition, in addition to approaches that leverage existing therapeutics to develop new treatment options for patients. Significant advances in the future await a better understanding of the underlying pathophysiology of these conditions and of the neurobiological alterations associated with these disorders. It is hoped that some of the research directions described herein will stimulate additional research in this area and thereby help foster the discovery of novel agents for treating major sleep disorders.

Behavior vs. introspection: refining prediction of clinical depression via smartphone sensing data

Depression is a serious health disorder. In this study, we investigate the feasibility of depression screening using sensor data collected from smartphones. We extract various behavioral features from smartphone sensing data and investigate the efficacy of various machine learning tools to predict clinical diagnoses and PHQ-9 scores (a quantitative tool for aiding depression screening in practice). A notable feature of our study is that we leverage a dataset that includes clinical ground truth. We find that behavioral data from smartphones can predict clinical depression with good accuracy. In addition, combining behavioral data and PHQ-9 scores can provide prediction accuracy significantly exceeding each in isolation, indicating that behavioral data captures relevant features that are not reflected by PHQ-9 scores. Finally, we develop multi-feature regression models for PHQ-9 scores that achieve significantly improved accuracy compared to direct regression models based on single features.

Sleep Disturbances in Patients with Medical Conditions.

Sleep-wake cycle disturbances are prevalent in patients with medical conditions and frequently present as part of a symptom cluster. Sleep disturbances impair functioning and quality of life, decrease adherence to treatments of the primary medical condition, and increase morbidity and mortality. The pathophysiology of sleep disturbances in these patients involves alterations in immune and neuroendocrine function and shares common pathophysiologic pathways with comorbidities such as fatigue and depression. Emphasis is placed on the evaluation and management of medical and psychiatric comorbidities and other factors contributing to sleep problems. Primary treatments include cognitive-behavioral therapy and pharmacotherapy.

Thyrotropin-Releasing Hormone Can Relieve Cancer-Related Fatigue: Hypothesis and Preliminary Observations

Fatigue in cancer patients is highly prevalent, predominantly idiopathic, difficult to manage, and has a significant negative impact on quality of life. Thyrotropin-releasing hormone (TRH) exerts normotrophic, state-dependent therapeutic effects in a variety of experimental and clinical situations. To evaluate TRH as a treatment for cancer-related fatigue, an ongoing randomized, placebo-controlled, crossover pilot study of breast cancer patients has been initiated and this report presents preliminary observations conducted with three of these patients over 4 consecutive weeks, thereby involving a total of six TRH treatments and six saline controls. Global assessment using both subjective and objective parameters showed that TRH exerted clear anti-fatigue effects in four of the six TRH treatments. These responses were rapid in onset and persisted through the 24 h observation period. No anti-fatigue responses were seen in five of the six saline controls. No unexpected side-effects were seen with TRH administration. These initial findings support the proposal that TRH can ameliorate cancer-related fatigue.

Sleep Disturbances in Schizophrenia

Sleep disturbances are prevalent in patients with schizophrenia and play a critical role in the morbidity and mortality associated with the illness. Subjective and objective assessments of sleep in patients with schizophrenia have identified certain consistent findings. Findings related to the sleep structure abnormalities have shown correlations with important clinical aspects of the illness. Disruption of specific neurotransmitter systems and dysregulation of clock genes may play a role in the pathophysiology of schizophrenia-related sleep disturbances. Antipsychotic medications play an important role in the treatment of sleep disturbances in these patients and have an impact on their sleep structure.

Algorithm-Driven Pharmacological Management of Bipolar Disorder in Connecticut Prisons

The objective of this study was to assess adaptation of the Texas Implementation of Medication Algorithm (TIMA) for bipolar disorder (BD) in the Connecticut Department of Correction. A nonrandomized sample of 20 males and 20 females, with diagnoses of BD Type I or II, was enrolled in the study. Two TIMA-trained psychiatrists treated the participants over a 12-week period following the TIMA protocol. The primary outcome measure was the Bipolar Disorder Symptom Scale. Secondary outcome measures evaluated global clinical status, comorbid symptomatology, and quality of life. Significant improvement was seen with the primary and secondary outcome measures (p < .001). Subanalyses showed differences in outcomes based on gender and whether a manic or depression algorithm was used. Antidepressant and antipsychotic medication use decreased, with increase in anticonvulsant and anxiolytic medication usage. This pilot study confirmed the effectiveness and benefits of TIMA for BD adaptation in the correctional setting.

Best practices: disseminating best practices for bipolar disorder treatment in a correctional population.

Use of medication treatment algorithms may facilitate clinical decision making, improve consistency, and reduce polypharmacy in the correctional setting. A feasibility study was conducted investigating use of Texas Implementation of Medication Algorithms (TIMA) guidelines for bipolar disorder in the Connecticut Department of Correction. Forty inmates with diagnoses of bipolar disorder were treated over a 12-week period adhering to the TIMA algorithm for bipolar disorder. Significant improvement was seen in the primary and secondary outcome measures (p<.001). This pilot project confirmed the feasibility of algorithm adaptation to the correctional setting and provided specific recommendations for successful dissemination of the TIMA algorithm for bipolar disorder in correctional settings.

The effect of typical and atypical antipsychotic drugs on sleep of schizophrenic patients

Patients with schizophrenia commonly report problems related to disturbed sleep, most often presenting as difficulties with sleep onset latency (SOL) or with sleep maintenance, whereas others have identified disrupted circadian sleep control such as phase delay and even free running cycles. Several studies have evaluated objective measures of sleep abnormalities in patients with schizophrenia by means of polysomnographic techniques. While the majority of published reports are associated with substantial methodological problems that confound interpretation of the data presented, some consistent patterns of findings can be observed across a number of studies examining sleep physiology in schizophrenic patients. The most consistently reported findings have included prolonged SOL and increased wake time after sleep onset (WASO). Additionally, some studies reported diminished slow-wave sleep (SWS) time in patients with schizophrenia as compared to healthy controls, and other studies noted short REM latency (REM-L). However, the latter two findings were not as consistently replicated across studies. Considerable progress has been made in recent years in delineating neurobiological mechanisms involved in the regulation of sleep and wake states as well the coordination of transitions within sleep from one state to another (e.g., regulating transitions from non-REM to REM sleep stages). In addition to the major excitatory and inhibitory neurotransmitter systems glutamate and GABA, monoamine neurotransmitter systems, including dopamine (DA), norepinephrine (NE), serotonin (5-HT), acetylcholine (ACh) and histamine have all been demonstrated to play important roles in the sleep state regulation process. Antipsychotic drugs, including both the typical and atypical antipsychotic classes, have all been shown to produce prominent inhibitory effects at DA D2 receptor sites. Additionally, to varying degrees, different antipsychotic drugs produce modulatory effects on 5-HT, NE, ACh and histaminergic receptors, thereby providing a strong rationale for anticipating prominent effects of antipsychotic drugs on sleep physiology when administered to patients with schizophrenia, other psychiatric disorders as well as to healthy control subjects. A number of studies have reported data on effects of antipsychotic drugs on sleep measures in patients with psychiatric disorders and in healthy control groups. Many of the published reports are noted to have significant methodological limitations, making interpretation of the findings tenuous in some cases. Nevertheless, some consistent patterns of findings have been reported to date. In general, administration of typical antipsychotic drugs has been noted to result in improved sleep continuity, as characterized by increased total sleep time, increased sleep efficiency and decreased SOL and WASO. In these studies, SWS was generally not altered but REM-L was occasionally increased. In studies examining effects of the atypical antipsychotic drugs, generally similar patterns of improvement of sleep continuity measures have been reported across the various agents in this class, but some differences have been noted in terms of effects on SWS and on parameters of REM activity. Differences in effects of various atypical antipsychotic drugs on sleep may be explained by their differing pharmacological mechanisms of action. Substantial limitations are noted in terms of the studies of effects of atypical antipsychotic drugs on sleep. For several of the drugs in this class, no published studies have characterized their effects in the clinical populations in which they are used most extensively. Thus, there is a need for much further work in this area of great clinical importance.