ABSTRACT
OBJECTIVE: The aim of this open-label naturalistic study was to assess clinical outcomes and the predictive value of duloxetine plasma levels in major depressive disorder in the elderly. METHODS: This naturalistic, open-label design involved 35 outpatients aged between 65 and 87 years. Duloxetine plasma levels were collected in 24 patients after the first month. Patients were evaluated using 21-item Hamilton Rating Scales for Depression, Hamilton Rating Scales for Anxiety, the Clinical Global Impression Severity, Mini Mental State Examination, Cumulative Illness Rating Scale, Barthel Index and Beck's Depression Inventory. RESULTS: Duloxetine plasma levels at T2 ranged from 4.9 to 201.9 ng/mL without a significant correlation between duloxetine dose and plasma levels. A significant improvement in mean 21-item Hamilton Rating Scales for Depression total scores at T2,T3, T4, T9 and T12 and a progressive significantly decrease of the mean Hamilton Rating Scales for Anxiety scores from T3 to T12 were observed. CONCLUSIONS: The levels of duloxetine in plasma do not correlate with a greater clinical improvement, indeed appear to adversely affect the improvement of the Beck Depression Inventory and Hamilton Rating Scales for Anxiety. This could be explained by an increase in side effects that may aggravate the discomfort felt by the patient. Copyright © 2016 John Wiley & Sons, Ltd.
Subject(s)
Depressive Disorder, Major/drug therapy , Duloxetine Hydrochloride/administration & dosage , Serotonin and Noradrenaline Reuptake Inhibitors/administration & dosage , Age Factors , Aged , Aged, 80 and over , Depressive Disorder, Major/physiopathology , Dose-Response Relationship, Drug , Duloxetine Hydrochloride/adverse effects , Duloxetine Hydrochloride/pharmacokinetics , Female , Humans , Male , Predictive Value of Tests , Psychiatric Status Rating Scales , Serotonin and Noradrenaline Reuptake Inhibitors/adverse effects , Serotonin and Noradrenaline Reuptake Inhibitors/pharmacokinetics , Treatment OutcomeABSTRACT
RATIONALE: It is still common to encounter a partial or no response to antipsychotic treatment in clinical practice, but only individual case reports are currently available concerning the efficacy of long-acting risperidone (RLAI) in treatment-resistant schizophrenia. The relationship between RSP and 9-OH-RSP plasma levels, and clinical response or tolerability has not yet been thoroughly assessed. METHODS: This open-label, non-randomised study involved 30 outpatients with treatment-resistant schizophrenia, who were prescribed RLAI for 6 months, and clinically evaluated using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression-Improvement Scale (CGI-I), and the Simpson and Angus Scale for Extrapyramidal Side Effects (EPSE). Plasma RSP and 9-OH-RSP levels were determined at steady-state, and the metabolic ratio (MR) was calculated as plasma 9-OH-RSP/RSP levels. RESULTS: At the end of the study, 60% of the patients responded to RLAI (a >or=20% reduction in the PANSS score). Linear regression analysis showed a significant positive relationship between the RSP dose and active moiety (RSP + 9-OH-RSP) (r = 0.4; p = 0.02). There was a significant positive relationship between active moiety and EPSE scores (r = 0.6; p = 0.00). The BPRS responders had a significantly higher mean MR than the non-responders (3.41 +/- 1.87 SD vs 1.60 +/- 0.98 SD) (p = 0.00). CONCLUSIONS: Therapeutic drug monitoring seems to be useful in optimising the dose of RLAI, especially in the case of tolerability problems. MR might be a better index of clinical response to RLAI than the value of the active moiety, although this needs to be confirmed by further data.
