Safety and Efficacy of Add on Modafinil to Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder (original) (raw)
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Advances in Therapy, 2006
Despite the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depression, a significant number of patients show partial or no remission of symptoms. Some evidence suggests that psychostimulant augmentation may be helpful in treating patients with residual symptoms of depression. The efficacy of modafinil in augmenting SSRIs in depressed patients with residual fatigue or excessive daytime sleepiness has yet to be systematically investigated. In a series of 25 patients with major depressive disorder, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, who showed significant residual symptoms after an adequate SSRI trial (12 wk) and who were evaluated according to the Fatigue Severity Scale (FSS), subjects with scores ≥4 were given open-label modafinil augmentation for a minimum of an additional 6 wk. Treatment response was assessed prospectively with the FSS, the Epworth Sleepiness Scale (ESS), and the Hamilton Rating Scale for Depression (HAM-D) during the first visit and at the second and sixth weeks. Twenty-one of 25 patients in this series who were treated with modafinil and SSRIs completed the 6-wk augmentation trial. At end-point assessment, all patients showed significant improvement in fatigue and sleepiness in FSS and ESS scores, as well as in Advances in Therapy ® Transmission and reproduction of this material in whole or part without prior written approval are prohibited. 646 0900 HAM-D scores (P<.01). In the second week, 29.4% of patients had a HAM-D score <7, which was defined as remission; this rate was 64.7% in the sixth week. The rate of patients whose HAM-D score dropped by more than 50%, defined as responders to treatment, was 41.1% and 76.4% in the second and sixth weeks, respectively. Results of this preliminary, open-label trial suggest that modafinil may be effective in augmenting ongoing SSRI treatment for a portion of patients with major depression who have residual fatigue and sleepiness. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of modafinil augmentation of SSRI treatment in these patients.
Modafinil Augmentation Therapy in Unipolar and Bipolar Depression
The Journal of Clinical Psychiatry, 2013
Objective: Current pharmacologic treatments for a depressive episode in unipolar major depressive disorder (MDD) and bipolar depression are limited by low rates of remission. Residual symptoms include a persistent low mood and neurovegetative symptoms such as fatigue. The objective of this study was to examine the efficacy and tolerability of augmentation of first-line therapies with the novel stimulantlike agent modafinil in MDD and bipolar depression.
1006. Effects of Modafinil on Emotional Processing in Patients with Remitted Depression
Biological Psychiatry, 2017
BACKGROUND: Cognitive dysfunction is a core feature of depression and tends to persist even after mood symptoms recover, leading to detrimental effects on clinical and functional outcomes. However, most currently available treatments have not typically addressed cognition. Modafinil has been shown to have beneficial effects on cognitive function and therefore has the potential to improve cognition in depression. The objective of this doubleblind, placebo-controlled study was to investigate the effects of modafinil on cognitive functions in patients with remitted depression. METHODS: In total, 60 patients with remitted depression participated in the study. Cognitive functions were evaluated with tests of working memory, planning, attention, and episodic memory from the Cambridge Neuropsychological Test Automated Battery at the baseline session and after treatment. A double-blind, randomized, placebo-controlled, parallel groups design was used to assess the effects of single-dose (200 mg) modafinil (n 5 30) or placebo (n 5 30) on cognition and fatigue. The main outcome measures were neurocognitive test scores from the Cambridge Neuropsychological Test Automated Battery. Visual analogue scales for subjective feelings and fatigue were used as secondary measures. RESULTS: The modafinil group had significantly better performance on tests of episodic memory (p 5 .01, η p 2 5 .10) and working memory (p 5 .04, η p 2 5 .06). Modafinil did not improve planning or sustained attention. CONCLUSIONS: This study suggested that modafinil (200 mg) could improve episodic memory and working memory performance in patients with remitted depression. Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.
Pharmacological Reports, 2014
Background: Modafinil is a wake-promoting agent that provides wide ranges of neurological effects. There is evidence that it can produce antidepressant effects. This study investigated the antidepressant effect of modafinil in the tail suspension (TST) in mice. Methods: Different doses of modafinil was intraperitoneally (ip) administrated and then animals were subjected to TST and/or open field test (OFT). Moreover, the implication of the dopaminergic neurotransmission in modafinil's antidepressant effect was studied. For this purpose, animals were pretreated with haloperidol (non-selective dopamine receptor antagonist), or SCH23390 and sulpiride (the dopamine D 1 and D 2 receptor antagonist, respectively), then were assessed by TST. The possible effect of sub-effective dose of modafinil in combination with sub-therapeutic doses of standard antidepressants was also evaluated in separate groups. Results: Modafinil (75 mg/kg, ip) produced antidepressant effect in TST, as compared to a control group, without any alterations in ambulation in OFT. Pretreatment of mice with haloperidol (0.2 mg/kg, ip) and sulpride (50 mg/kg, ip) blocked the anti-immobility effect of modafinil (75 mg/kg, ip). We also found that the administration of SCH23390 (0.05 mg/kg, sc) couldn't antagonize the antidepressant effects of modafinil. In addition, a sub-effective dose of modafinil (50 mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1 mg/kg, ip), fluoxetine (1 mg/kg, ip) and imipramine (0.1 mg/kg, ip) and reduced immobility time in TST. Conclusion: Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D 2 receptors) system.
Adjunctive use of modafinil in bipolar patients: just another stimulant or not
Current Psychiatry Reports, 2008
Depression is much more common in the life course of people with bipolar disorder than mania or mixed states. Unfortunately, few established treatments are available, and new ones are needed. Modafinil is a novel stimulant approved for treating improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder. Given that bipolar depression is commonly associated with fatigue and somnolence, modafinil is a logical choice. In one recent study of moderate size (n = 85), modafinil was shown to be more effective than placebo in treating bipolar depression. The incidence of cycle induction in this trial was very low (lower than placebo), although isolated case reports of mania, hypomania, or mixed states have been reported. Given the limited options for bipolar depression, modafinil should be considered in patients who have not responded to approved treatments, although more research is needed.