Kathryn M. Schak

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.

Family functioning and maternal distress in adolescent girls with anorexia nervosa

OBJECTIVE To determine the nature of family distress in families of girls with anorexia nervosa (AN), this study compared aspects of family functioning in adolescent girls with AN to girls with a chronic illness and girls without a condition. METHOD Participants consisted of 25 adolescent girls with a primary DSM-IV diagnosis of AN, 20 girls with an ICD-10 diagnosis of insulin dependent diabetes mellitus (IDDM), and 20 girls from the community. Mothers and daughters completed questionnaires of family functioning and psychological symptoms. RESULTS When compared with mothers of daughters with IDDM, families of girls with AN experienced greater family conflict, reduced parental alliance, and increased feelings of depression. However, once the emotional impact of the illness on the mothers was statistically controlled, group differences were no longer significant. DISCUSSION Family distress and dysfunction may reflect an accommodation process that occurs in families living with a child with AN.

The Role of Gabapentin in the Management of Alcohol Withdrawal and Dependence

Objective: To review the literature evaluating gabapentin for alcohol withdrawal and dependence. Data Sources: A literature search of MEDLINE (1966 to end of March 2015) and PubMed was performed using the terms alcohol, gabapentin, withdrawal, and dependence. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: English-language prospective studies evaluating gabapentin for alcohol withdrawal and dependence were evaluated. Data Synthesis: A total of 10 publications utilizing gabapentin in alcohol withdrawal (n = 5) and alcohol dependence (n = 5) were included in this review. Limited data suggest that gabapentin can provide benefit in managing mild alcohol withdrawal syndrome. There were 5 reported or suspected seizures in the withdrawal studies, suggesting that additional safety data are necessary before gabapentin monotherapy can be routinely considered. Sleep and mood/anxiety-related outcomes were positively influenced by gabapentin, which may result in long-term benefits if continued beyond the withdrawal period for the treatment of alcohol dependence. Studies evaluating gabapentin for alcohol dependence demonstrated dose-dependent benefits for complete abstinence, rates of no heavy drinking, and cravings. Gabapentin used to treat alcohol dependence was well tolerated with no severe adverse reactions reported in the extant literature. Conclusion: Gabapentin may have a role in the treatment of mild alcohol withdrawal, but future studies should focus on adequate dosing strategies. Gabapentin should be considered for the treatment of alcohol dependence when barriers prevent the use of traditional agents. Additional studies should be conducted to further validate findings from the research conducted to date, but the current literature is promising for gabapentin in the treatment of alcohol dependence.

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

Continuation phase intravenous ketamine in adults with treatment-resistant depression.

BACKGROUND Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. METHODS Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only). RESULTS Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up. LIMITATIONS This was an uncontrolled feasibility study with a small sample size. CONCLUSIONS The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS. GOV IDENTIFIER NCT02094898.

Minority primary care patients with depression outcome disparities improve with collaborative care management

Background/Objectives:Racial and ethnic disparities in depression incidence, prevalence, treatment, and outcomes still persist. The hypothesis of this study was that use of collaborative care management (CCM) in treating depressed primary care patients would decrease racial disparities in 6-month clinical outcomes compared with those patients treated with usual primary care (UC). Research Design/Subjects:In a retrospective chart review analysis, 3588 (51.2%) patients received UC and 3422 (48.8%) patients were enrolled in CCM. Logistic regression analyses were used to examine disparities in 6-month outcomes. Results:Minority patients enrolled in CCM were more likely to be participating in depression care at 6 months than minority patients in UC (61.8% vs. 14.4%; P⩽0.001). After adjustment for demographic and clinical covariates, this difference remained statistically significant (odds ratio=9.929; 95% CI, 6.539–15.077, P⩽0.001).The 568 minority UC patients with 6-month follow-up PHQ-9 data demonstrated a much lower odds ratio of a PHQ-9 score of <5 (0.220; 95% CI, 0.085–0.570; P=0.002) and a much higher odds ratio of PHQ-9 score of ≥10 (3.068; 95% CI, 1.622–5.804; P<0.001) when compared with the white, non-Hispanic patients. In contrast, the 2329 patients treated with CCM, the odds ratio for a PHQ-9 score of <5 or ≥10 after 6 months, demonstrated no significance of minority status. Conclusions:Utilization of CCM for depression was associated with a significant reduction of the disparities for outcomes of compliance, remission, or persistence of depressive symptoms for minority patients with depression versus those treated with UC.

Gender differences in the association of agitation and suicide attempts among psychiatric inpatients

OBJECTIVE To determine if the relationship of agitation with suicide ideation and suicide attempts differed between men and women. METHOD Self-reported severity of agitation and other suicide risk factors was obtained from 7698 consecutive patients during admission for inpatient psychiatric treatment during a 5-year period. RESULTS Agitation was highest among men with a history of suicide attempts. Agitation was significantly associated with frequency of suicide ideation and history of suicide attempt, but the gender-by-suicide interaction was only significant as a predictor of suicide attempt history. For men, agitation was associated with significantly increased risk for suicide attempt, but for women, agitation was not associated with risk for suicide attempt history. Results were unchanged when analyses were repeated among the subgroup of patients with suicide ideation. CONCLUSIONS Agitation is associated with history of suicide attempt among male but not female psychiatric inpatients. Agitation differentiates between those men who have only thought about suicide and those who have made suicide attempts.

Aripiprazole-Associated Hiccups A Case and Closer Look at the Association Between Hiccups and Antipsychotics

Aripiprazole’s pharmacologic properties (including dopamine 2 and 5-hydroxytryptamine 1A [5HT1A] receptor partial agonism and 5HT2A receptors antagonism) may be associated with the onset of hiccups. Case Description: A 21-year-old, antipsychotic-naive patient with bipolar I disorder and remote brain trauma developed persistent hiccups following aripiprazole titration. Despite trials of metoclopramide and chlorpromazine, hiccups continued. Remission of hiccups occurred with discontinuation of aripiprazole. Discussion: The exact etiology of hiccups is unknown but likely involves dopamine and/or γ-butyric acid. Highlighting the uncertainty related to drug-induced hiccups is the fact that multiple antipsychotics have been reported to not only induce hiccups but also to alleviate them. As the development of persistent hiccups may result in extensive medical workup, clinicians should be aware of drug-associated causes including aripiprazole.

Use of the Suicide Status Form-II to investigate correlates of suicide risk factors in psychiatrically hospitalized children and adolescents

BACKGROUND Suicide is the third leading cause of death in the United States for youth 12-17 years or age. Acute psychiatric hospitalization represents a clear worst point clinically and acute suicide risk is the most common reason for psychiatric admission. We sought to determine factors associated with differences in individual suicide risk assessment for children and adolescents during acute psychiatric admission. METHODS Study participants were 1153 youth consecutively admitted to an inpatient psychiatry unit who completed a self-administered Suicide Status Form (SSF) within 24h of admission. Additional information on suicide risk factors was obtained through medical chart abstraction. RESULTS Females reported significantly greater psychological pain, stress, hopelessness, and self-hate on the SSF and were significantly more likely to have made a suicide attempt just prior to the index hospital admission (OR=1.59, SE=0.29; CI=1.12-2.26), report a family history of suicide (OR=2.02, SE=0.33; CI=1.47-2.78), and had experienced a greater number of inpatient psychiatry admissions related to suicidal ideation (RR=1.33, SE=0.13; CI=1.10-1.61). High school aged youth and those with a primary diagnosis of depression displayed consistently elevated SSF scores and risk factors for suicide compared to comparison groups. LIMITATIONS Diagnosis was determined through chart abstraction. Responses to access to firearm question had missing data for 46% of the total sample. CONCLUSIONS Systematic administration of a suicide-specific measure at admission may help clinicians improve identification of suicide risk factors in youth in inpatient psychiatry settings.

The Perils of Illegitimate Online Pharmacies: Substance-Induced Panic Attacks and Mood Instability Associated With Selegiline and Phenylethylamine

The recent rise in public access to illegitimate online pharmacies providing unrestricted access to psychotropic medications, in combination with the growing availability of substances that can produce legal highs, poses a significant risk to patients. This report describes a case of substance-induced depression and panic attacks associated with illegitimately obtained selegiline used in combination with the health supplement phenylethylamine (PEA).