Simon Kung

Serial infusions of low-dose ketamine for major depression

Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. Results: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

A Psychometric Investigation of the Suicide Status Form II with a Psychiatric Inpatient Sample.

We investigated the psychometric validity and reliability of the Suicide Status Form-II (SSF-II) developed by Jobes, Jacoby, Cimbolic, and Hustead (1997). Participants were 149 psychiatric inpatients (108 suicidal; 41 nonsuicidal) at the Mayo Clinic. Each participant completed assessment measures within 24 hours of admission and 48-72 hours later. Factor analyses of the SSF core assessment produced a robust two-factor solution reflecting chronic and acute response styles. The SSF core assessment had good to excellent convergent and criterion validity; pre-post SSF ratings also demonstrated moderate test-retest reliability. The results replicated previous research and show that the SSF-II is psychometrically sound with a high-risk suicidal inpatient sample.

A randomized comparison of ketamine versus methohexital anesthesia in electroconvulsive therapy.

To assess the clinical utility of ketamine as an anesthetic agent for electroconvulsive therapy (ECT), based upon recent findings that ketamine may have antidepressant properties. Depressed ECT patients were randomly assigned to receive anesthesia with either ketamine or methohexital. Outcome measures included assessments of depressive severity, cognition, post-anesthesia side effects, and hemodynamics. Twenty one patients were treated with ketamine and 17 with methohexital. There were no significant differences in depression or cognitive outcomes between the two drugs. Additionally, there were no measures of post-anesthesia tolerability or hemodynamics which favored ketamine. Ketamine anesthesia does not accelerate the antidepressant effect of ECT or diminish the cognitive side effects, at least as measured in this study. Furthermore, there is no apparent benefit of ketamine for speed or quality of post-ECT recovery, and it is associated with higher systolic blood pressures after the treatments. Ketamine is associated with longer motor seizure duration than methohexital.

Treatment of Nightmares With Prazosin: A Systematic Review

Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in todays world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports.

Relationship of optimism-pessimism and health-related quality of life in breast cancer survivors

ABSTRACT Few studies have investigated the influence of optimism–pessimism in breast cancer survivors. This study used a retrospective design with 268 adult women who completed the Minnesota Multiphasic Personality Inventory (MMPI) as part of their medical care approximately 10 years prior to their breast cancer diagnosis and Medical Outcome Study Short-Form General Health Survey (SF-36 or SF-12), on average, 8 years after diagnosis. MMPI pessimism scores were divided into quartiles, and t tests were used to determine differences between those highest and lowest in pessimism on health-related quality-of-life (QOL) measures, demographics, and disease status. The mean age at diagnosis of breast cancer was 63 years, and 74% had early-stage breast cancer. Patients age 65 years and older were significantly lower on physical health–related QOL scales. There were no significant differences in health-related QOL scores by stage of disease. Patients with a pessimistic explanatory style were significantly lower on all of the health-related QOL scores, compared to those with a nonpessimistic style. Breast cancer survivors who exhibit a pessimistic explanatory style report lower health-related QOL for years after receiving a cancer diagnosis, compared to nonpessimistic women.

The use of slow-frequency prefrontal repetitive transcranial magnetic stimulation in refractory neuropathic pain

Objective: A number of antidepressant medications, as well as electroconvulsive therapy, have been shown to reduce chronic pain. Slow-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex has also been shown to have an antidepressant effect. Given the high degree of suffering experienced by subjects with chronic neuropathic pain and the treatment resistance noted in this population, the use of slow-frequency rTMS as adjuvant therapy may be of significant clinical benefit. Methods: Fifteen sessions of 1-Hz rTMS (1600 stimulations/session) were applied to the right dorsolateral prefrontal cortex as adjuvant treatment in 9 subjects with refractory neuropathic pain over 3 weeks. Pain and depression ratings were performed at baseline, weekly during rTMS treatment, and monthly for up to 3 months after treatment. Results: Five males and 4 females participated, and all had longstanding refractory neuropathic pain (range, 1-19 years), with an average baseline pain rating of 7.3 and no depression (Hamilton Rating Scale for Depression average, 3.6; range, 0-8). Three subjects had a greater than 50% decline in pain ratings by the completion of rTMS treatments, and 1 subject responded more slowly with greater than 50% improvement in pain by the end of the 3-month follow-up. An improvement in pain ratings was noted in responders within the first week. Conclusions: Although these are preliminary findings in an open treatment trial, the subjects in this trial are among the least likely to have a placebo response. Given that rTMS is a well-tolerated and noninvasive intervention, any sustained improvement in neuropathic pain with rTMS is encouraging.

Association of Optimism-Pessimism With Quality of Life in Patients With Head and Neck and Thyroid Cancers

OBJECTIVE To examine the relationship between optimism-pessimism and quality of life (QOL) in survivors of head and neck and thyroid cancers. PATIENTS AND METHODS Between 1963 and 2000, 190 patients completed both the Minnesota Multiphasic Personality Inventory (MMPI), used to assess explanatory style (optimism-pessimism), and either the 12-Item or 36-Item Short-Form Health Survey (SF-12 or SF-36), used to assess QOL. The MMPIs were completed an average of 13.4 years before the QOL assessment. The QOL measures were completed an average of 12.5 years after cancer diagnosis. Patients were divided into quartiles based on their MMPI Optimism-Pessimism scale score. Analysis was performed for all patients, those with head and neck cancer, and those with thyroid cancer. Adjustments were made for age, sex, and disease stage. RESULTS For all 190 patients, optimism was associated with a higher QOL on both the mental and the physical component scales and 6 of 8 subscales of the SF-12 and SF-36. For patients with head and neck cancer, optimism was associated with higher QOL on 3 subscales but neither component scale. For patients with thyroid cancer, optimism was associated with higher QOL on both component scales and 6 subscales. After adjusting for age, sex, and disease stage, optimism was not associated with QOL in the head and neck cancer group. CONCLUSIONS Optimism was associated with a higher QOL in survivors of thyroid cancer compared with survivors of head and neck cancer. After adjusting for age, sex, and disease stage, optimism was not associated with QOL for survivors of head and neck cancer. Optimism was more associated with the mental rather than physical QOL subscales.

Pharmacogenomics of antidepressant induced mania: A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association

BACKGROUND Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. METHODS Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. RESULTS Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. LIMITATIONS Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. CONCLUSIONS There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).

Potential Risks of Poorly Monitored Ketamine Use in Depression Treatment.

At the time of his initial presentation to a tertiary medical center in 2012, “Mr. A” was a 52-year-old divorced man with a 30-year history of recurrent major depressive disorder, persistent depressive disorder, and a remote history of outpatient treatment for alcohol use disorder as a young adult. His first episode of major depression occurred at age 22 in association with a suicide attempt (he jumped off a four-story building) and subsequent hospitalization. Mr. A’s medical history was significant for corrected hypothyroidism. The prospective course of illness encompassed four subsequent psychiatric admissions at our medical center, annually from 2012 to 2014, illustrating clear treatment-resistant depression and a reemerging pattern of substance misuse (alcohol, benzodiazepines, and ketamine). Mr. A’s admission in the summer of 2012 focused on consultation for depression and consideration of ECT. Prior medication trials of optimal dose and duration included trazodone, escitalopram, bupropion, and mirtazapine with lamotrigine and aripiprazole augmentation strategies. Mr. A reported negligible alcohol consumption (a single drink on rare occasions). He received seven bilateral ECT treatments, and his symptoms improved; his score on the Hamilton Depression Rating Scale declined from 37 on admission to 8 at discharge. He was discharged after 18 days on mirtazapine monotherapy with recommendations to maximize his dosing of mirtazapine and to add lithium for augmentation following his ECT course. HereceivedthreeadditionalECTtreatmentspriortoself

Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders.

The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.