The term “resistant” does not usually bode well in the healthcare setting. “Antimicrobial resistant,” “resistant to care,” “chemotherapy resistant cancer”—all of these may prompt specific focused interventions or programs, often involving multi-disciplinary team approaches, and creative, out-of-the box solutions, to attempt achievement of positive outcomes for the patients involved. Treatment-resistant depression is no different. It is a diagnosis that is often dreaded by patients, caregivers, and providers alike. It is responsible for increased hospitalizations, increased outpatient provider visits, greater use of psychotropic medications, and an average six times greater total healthcare cost incurrence compared to non-treatment-resistant depressed patients.1
This toolbox compares pharmacologic options for treatment-resistant depression (TRD) that may be considered if the patient fails to experience adequate response or remission despite optimizing antidepressant therapy.
BF is a 42 year-old Caucasian male who reported his onset of depression began four years ago after he was involved in a car accident that fractured his hip. He was not treated for depression until he overdosed on approximately 50 aspirin 325 mg tablets and 750 ml of whiskey (seven months following the accident). After being medically cleared from the emergency room and acute inpatient unit, he was transferred to inpatient psychiatry for evaluation of depression. Upon admission to the inpatient psychiatric unit, his labs were found to be within normal limits (WNL) except a slight elevation inCASE
Major depressive disorder is a serious, recurrent condition with significant impact on a person's quality of life and functioning, which carries a significant risk of premature death due to suicide. There is evidence that supports the effectiveness of lithium as an augmentation strategy for treatment-resistant depression, as well as for reducing suicidality in this population. This review introduces several theories regarding the proposed mechanism behind lithium's anti-suicidal effects and summarizes a selection of the pertinent literature supporting lithium's beneficial effects on suicidality.
Despite new insights and evidence-based treatment options for clinical depression in the recent years, the current choices of safe and effective therapies are still inadequate to sustain a long-term response in the depressed patient. Many do not improve, improve partially or are classified as ‘treatment resistant’ with poor compliance and marked functional impairment. The aim of this article is to review future therapeutic options and advances in treatments available for this cohort of patients. Several innovative and promising studies are underway to explore the role of ketamine, a glutamate N-methyl-d-aspartate (NMDA) antagonist in treating treatment-resistant depression and acute suicidal ideation. Furthermore, new research reveals that depression is associated with a significant drop in neurotrophic factors such as brain derived neurotrophic factor (BDNF) and increasing BDNF may be a new strategy for developing new antidepressants. Neuromodulation interventions by stimulating specific brain regions including deep brain stimulation (DBS), magnetic seizure therapy (MST), and transcranial direct current stimulation (tDCS), still in experimental stages, are also discussed.
There has been a recent increase in public awareness of the drug 3,4-methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy. A purified version of this drug, known as “Molly”, is perceived by users to be safer than other illicit drugs, as it is expected to be free of toxic adulterants. This article reviews the clinical effects and toxicity associated with MDMA, as well as data on the purity of Molly and Ecstasy.
The percentage of patients who have failed to completely or partially respond to multiple trials of antidepressants at adequate doses and for an adequate duration of therapy has varied in the literature and is considered substantial. Numerous strategies exist to treat poor antidepressant response, but often medications are selected on a “trial and error” basis. Genetic factors may play a role in poor response or intolerance to treatment with antidepressants which lead to treatment failures. Currently, available genetic testing as well as genetic testing currently under research may help guide clinicians with proper medication and dose selection.
Mood disorders are highly prevalent throughout the United States, and high rates of relapse, recurrence, and treatment failure lead to treatment resistance. This article will review the available literature and treatment recommendations for treatment resistant mood disorders in special populations including: geriatrics, children and adolescents, pregnancy, and comorbid substance use disorders.
Many of the second generation antipsychotics (SGAs) have been studied as adjunctive agents in the management of treatment-resistant major depressive disorder. Two have also been examined for use as monotherapy for depression. Currently, aripiprazole, olanzapine (in combination with fluoxetine), and quetiapine XR are approved by the FDA for use as adjunctive agents in the treatment of major depressive disorder, and no SGAs are FDA-approved as monotherapy for the disorder. This article reviews the available evidence regarding the use of SGAs in patients with treatment-resistant major depressive disorder and the subsequent role for these agents based on this evidence. There is evidence that aripiprazole, quetiapine, olanzapine, and risperidone can be effective in improving depressive symptoms when added to antidepressant therapy, but the benefits have to be weighed against their risk of producing serious adverse effects.
Introduction
. Although not definite, studies are finding Alzheimer's disease may be related to loss of cholinergic innervation. In order to impact this loss of function, therapeutic agents have been developed to reduce the breakdown of acetylcholine, a neurotransmitter vital in cognitive processes. Donepezil has been used in Alzheimer's disease for improving cognition. Although the package insert suggests nighttime administration to reduce the instance of daytime side effects, some patients report sleep disturbances.
Methods
. Patient charts at the Tallahassee Memorial Healthcare Neuroscience Center (TMH-NSC) were reviewed. Charts of those patients who met the inclusion criteria were used to determine the correlation between night time administration of donepezil and sleep disturbances.
Results
. A total of 186 patient charts were analyzed. Of those 186, 103 of the patients were taking donepezil as directed in the package labeling, at night time. Nearly half (47.6%) of the patients taking donepezil at night reported night time disturbances (NTD) and only 21 of the 83 patients taking donepezil in the morning reported NTD.
Conclusion
. This retrospective study showed that taking donepezil at night may be associated with sleep disturbances. Although labeling suggests administration in the evening, should NTDs occur, changing the medication administration to the morning should be explored before switching therapeutic agents.
Introduction: This study evaluated pharmacoeconomic considerations, specifically drug cost and patient readmission rates, of the non-formulary agent paliperidone palmitate, within the Alegent Creighton Health system. Pharmacy reimbursement rates for paliperidone palmitate are better on an outpatient versus inpatient basis. Given the low reimbursement rates for inpatient psychiatric care and the high cost of paliperidone palmitate, the drug cost could be justified if patients who received the injection demonstrated a subsequent reduction in readmission. Methods: The electronic medical record was used to identify patients who received at least one inpatient injection of paliperidone palmitate within the Alegent Creighton Health system from January 2010 – April 2012. Indication, dose, administration date, concurrent antipsychotics, length of stay (LOS), discharge date, and time to readmission were also recorded. Finance reports determined hospital cost and reimbursement for each inpatient stay and pharmacy cost of each paliperidone palmitate injection. Results: Thirty-two patients received paliperidone palmitate during the period specified. The average LOS was 18 days. The readmission rates for the paliperidone palmitate patients versus all patients at our institution with a diagnosis related group (DRG) of psychosis were as follows: within 30 days, 22% vs 12.5%; 60 days, 15% vs 15%; and 90 days, 25% vs 18%, respectively. The hospital experienced a net loss of roughly $5,610 per stay for the patients studied and paliperidone palmitate alone constituted approximately 16% of the total hospital cost per each patient stay. Discussion: In this limited patient population, it appears inpatient administration of paliperidone palmitate increased hospital cost without significantly reducing readmission rates at 30, 60, or 90 days post-injection. If patients are due for their monthly maintenance dose while hospitalized, the injection should be deferred to outpatient care if discharge is anticipated within one week since product labeling states maintenance injections can be given seven days after the monthly due date and outpatient reimbursement for the drug is superior.