A Placebo-Controlled Evaluation of Adjunctive Modafinil in the Treatment of Bipolar Depression

University of Freiburg, Freiburg, Baden-Württemberg, Germany
American Journal of Psychiatry (Impact Factor: 12.3). 09/2007; 164(8):1242-9. DOI: 10.1176/appi.ajp.2007.06060981
Source: PubMed


Modafinil is approved by the U.S. Food and Drug Administration for improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder. This study was conducted to evaluate the efficacy and safety of adjunctive modafinil in bipolar depression, which is often characterized by excessive sleepiness and fatigue.
Eighty-five patients with bipolar depression that was inadequately responsive to a mood stabilizer with or without concomitant antidepressant therapy were randomly assigned to receive adjunctive modafinil (N=41) or placebo (N=44) for 6 weeks. The primary outcome measure was baseline-to-endpoint change in score on the Inventory of Depressive Symptoms--Clinician Rated (IDS).
The baseline-to-endpoint change in IDS score was significantly greater in the modafinil group (mean dose, 177 mg/day) compared with the placebo group. Improvement in depressive symptoms was significantly greater in the modafinil group by week 2, and this greater improvement was maintained at weeks 4, 5, and 6. Both the response and remission rates were significantly higher in the modafinil group (44% and 39%) compared with the placebo group (23% and 18%). During the 6-week study period, there was no difference between groups in treatment-emergent hypomania or mania (six patients in the modafinil group and five in the placebo group) or hospitalization for mania (one in each group).
These data suggest that adjunctive modafinil at doses of 100-200 mg a day may improve depressive symptoms in patients with bipolar disorder.

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    • "Treatments for bipolar disorder : emphasis on bipolar depression Agents Indications in BD Status for bipolar depression References Antidepressants None for BD ; indication for 'major depression' widely assumed to include bipolar depression Clinically used Amit and Weizman (2012), Sidor and MacQueen (2011) (2012) Aripiprazole Mania, mixed-states and recurrences Mainly negative findings ; not approved for bipolar depression Thase et al. (2008) ; Cruz et al. (2010), De Fruyt et al. (2012) Asenapine Mania, mixed-states Experimental ; some evidence Cruz et al. (2010), De Fruyt et al. (2012) Carbamazepine Mania or mixed-states Not approved for bipolar depression Reinares et al. (2012) Deep brain stimulation Treatment-resistant depression Experimental ; some evidence Rizvi et al. (2011) Dopamine agonists a Proposed for bipolar depression Experimental ; some evidence Howland (2012) Divalproex Mania Not approved for bipolar depression Reinares et al. (2012) Electroconvulsive treatment Major and bipolar depression ; mania Clinically used ; FDA Class III medical device Dierckx et al. (2012) Gabapentin None for BD Not approved for bipolar depression Reinares et al. (2012) Glutamate NMDA-antagonists b Treatment-resistant & bipolar depression Experimental ; some evidence Owen (2012), Zarate et al. (2012) Lamotrigine Recurrences (mainly vs. depression) Not approved for bipolar depression Reinares et al. (2012) Levetiracetam None for BD Not approved for bipolar depression Saricicek et al. (2011) Light therapy (intensive) Depression, seasonal affective depression Experimental Poon et al. (2012) Lithium salts Mania, recurrences Not approved for bipolar depression Baldessarini (2013) Lurasidone Mania Not approved for bipolar depression De Fruyt et al. (2012) Modafinil, R-modafinil None for BD Experimental ; some evidence Frye et al. (2007) ; Calabrese et al. (2010) Olanzapine Mania, mixed-states, maintenance Some evidence ; approved in Japan Cruz et al. (2010), De Fruyt et al. (2012), Tohen et al. (2012) Olanzapine+Fluoxetine Treatment-resistant and acute bipolar depression FDA-approved Cruz et al. 2010, De Fruyt et al. 2012 Omega-3 fatty acids and other 'nutriceuticals' "

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    • "Mirroring these findings , in adults neither uncontrolled studies ( Carlson et al . 2004 ; El - Mallakh 2000 ; Fernandes and Petty 2003 ; Lydon and El - Mallakh 2006 ; Nasr et al . 2006 ) nor two controlled trials ( Calabrese et al . 2010 ; Frye et al . 2007 ) could detect a greater risk for ( hypo ) manic symptoms in bipolar depressed patients trea - ted with stimulants as add - on to mood stabilizers . There is more evidence suggesting that psychostimu - lants might be beneficial not only in patients with ADHD but also in those with mania . According to the vigilance model presented here "
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    • "In bipolar depression two trials showed some add-on effect of (ar)modafinil (Frye et al., 2007; Calabrese et al., 2010). Thus, one may assume that, in contrast to unipolar depression, bipolar patients may show some profit from stimulant add-on. "
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