Treatment Approach and Modalities for Management of Depression in Older People

Depression is common in older people, and while the approach to treatment is similar to a younger population, there are several additional treatment considerations to make based on comorbidities and cognitive impairment. Evidence-based psychotherapies such as cognitive behavioral therapy, interpersonal psychotherapy, and problem-solving therapy are recommended for mild-moderate depression in older people; however, the efficacy of these are limited in very old patients (older than 75 years of age) and those with cognitive impairment. Additionally, neuromodulation treatments such as electroconvulsive therapy and transcranial magnetic stimulation could prove beneficial for specific older people with depression. Use of pharmacotherapy that has demonstrated to be safe in older adults, as well as agents with adequate clinical experience in this population, should be considered based on patient-specific characteristics. Because of generally more complex medication regimens, risks of pharmacotherapy should be minimized with careful dosing strategies and special attention to avoid significant drug-drug interactions. While some data are available, antidepressant combination or augmentation strategies are less well studied in older people who fail to achieve remission or those with treatment-resistant depression, compared with younger populations.

Treatment Approach and Modalities for Management of Depression in Older People

Depression is common in older people, and while the approach to treatment is similar to a younger population, there are several additional treatment considerations to make based on comorbidities and cognitive impairment. Evidence-based psychotherapies such as cognitive behavioral therapy, interpersonal psychotherapy, and problem-solving therapy are recommended for mild-moderate depression in older people; however, the efficacy of these are limited in very old patients (older than 75 years of age) and those with cognitive impairment. Additionally, neuromodulation treatments such as electroconvulsive therapy and transcranial magnetic stimulation could prove beneficial for specific older people with depression. Use of pharmacotherapy that has demonstrated to be safe in older adults, as well as agents with adequate clinical experience in this population, should be considered based on patient-specific characteristics. Because of generally more complex medication regimens, risks of pharmacotherapy should be minimized with careful dosing strategies and special attention to avoid significant drug-drug interactions. While some data are available, antidepressant combination or augmentation strategies are less well studied in older people who fail to achieve remission or those with treatment-resistant depression, compared with younger populations.

Gastrointestial absorption of pimozide is enhanced by inhibition of P-glycoprotein

Following the death due to cardiac arrest of a patient taking pimozide, sertraline and aripiprazole antipsychotic/antidepressant combination therapy, a role of drug-drug interaction was suggested. Here, we investigated P-glycoprotein (P-gp)-mediated interaction among the three drugs using in vitro methods. Sertraline or aripiprazole significantly increased the permeability of pimozide in Caco-2 cell monolayers. ATPase assay indicated that pimozide is a P-gp substrate, and might act as a P-gp inhibitor at higher concentrations. The values of the kinetic parameters of carrier-mediated efflux, calculated from the concentration dependence of pimozide efflux from LLC-GA5-COL150 cells expressing human P-gp, were as follows: maximum transport rate (Jmax) = 84.9 ± 8.9 pmol/min/mg protein, half-saturation concentration (Kt) = 10.6 ± 4.7 μM, first-order rate constant (kd) = 0.67 ± 0.14 pmol/min/mg protein. Further, the efflux ratio of pimozide in LLC-GA5-COL150 cells was significantly decreased in the presence of sertraline or aripiprazole. These results indicate that pimozide is a substrate of P-gp, and its efflux is inhibited by sertraline and aripiprazole. Thus, P-gp inhibition by sertraline and/or aripiprazole may alter the gastrointestinal permeability of co-administered pimozide, resulting in an increased blood concentration of pimozide, which may increase the likelihood of pimozide’s known life-threatening side effect of QT prolongation.

Concurrent benzodiazepine use in older adults treated with antidepressants in Asia

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.Methods:The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.Results:The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.Conclusions:Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice.