Brief reportAbsence of mood switch with and tolerance to modafinil: A replication study from a large private practice
Introduction
Bipolar patients experience depression more often than mania (Judd et al., 2003). Fatigue has been reported as a possible clue for bipolarity when patients present with depression (Mitchell et al., 2001). Many stimulants or activating antidepressants used to address fatigue and depressed mood carry the risk of a switch into mania or hypomania in bipolar patients (Boerlin et al., 1998, Goldberg and Truman, 2003, Ghaemi et al., 2004).
Modafinil is a wake-promoting agent that is used to treat many conditions associated with fatigue, including depression (DeBattista et al., 2001, Nasr, 2004). Modafinil's mechanism of action is possibly mediated through the histamine receptors in the anterior hypothalamus without affecting the dopamine pathways associated with dependence and reward usually targeted by the stimulants (Lin et al., 1996). Modafinil, therefore, may be associated with a lower risk of mood switching in depressed patients.
Substance abuse is an additional contributing factor to mood switching. It is frequently comorbid with affective disorders raising additional concern for abuse of stimulants by bipolar patients. Modafinil is a class IV drug with the potential for risk of tolerance or abuse. However in previous studies of modafinil for depression augmentation, there were no reports of modafinil-induced mania in participants except for 4 single case reports of modafinil-induced recurrence of psychosis (Menza et al., 2000, DeBattista et al., 2001, Carlson et al., 2004, Nasr, 2004, Fava et al., 2005, Vorspan et al., 2005). There is also lack of evidence for its abuse potential even among cocaine dependent individuals (Warot et al., 1993).
The following study examines modafinil's effect on mood switching, dose stability, and abuse liability in a large series of affective disorder outpatients.
Section snippets
Method
A retrospective chart review was performed on all patients currently being seen in a private, rural, outpatient psychiatric office who received modafinil at some point during their treatment, usually as an adjunct to other medications. Data collected included patient demographics, MiniSCID diagnoses, clinical diagnoses including history of substance abuse, length and dosage of modafinil treatment, and concomitant use of mood stabilizers. Patients were monitored for manic or hypomanic symptoms
Results
Of approximately 1500 patient charts reviewed, 191 patients were given modafinil at some point during their treatment. There were 134 female patients, and 57 male patients. Over 95% of patients were Caucasian. The average age of all patients given modafinil was 49.3 (± 12.5, range: 20–82); 48.6 (± 13.4) for patients who quit within 2 months, and 49.8 (± 12.0) for patients who remained on at least 2 months. 31 patients had a clinical diagnosis of Bipolar I, 33 patients had a clinical diagnosis of
Discussion
The present findings indicated that modafinil did not induce manic/hypomanic switches or either tolerance or abuse in either unipolar or bipolar patients whether or not they had a positive history of chemical abuse/dependence.
Zis and Goodwin (1979) reported that cycle frequency increases with advancing age. This puts patients in this study at higher risk for mood switching yet 45 patients observed for 2 or more years did not show any mood cycling on modafinil (Zis and Goodwin, 1979).
Several
Conclusions
Modafinil can play an important role in the treatment of treatment-resistant depression and bipolar depression. This study demonstrates that adult affective disorder patients, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and sleepiness, without risking a switch in their mood or risk developing tolerance of this medication.
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2013, Journal of the Chinese Medical AssociationSuperior chronic tolerability of adjunctive modafinil compared to pramipexole in treatment-resistant bipolar disorder
2013, Journal of Affective DisordersCitation Excerpt :We found modafinil compared to pramipexole had significantly better longer-term tolerability (26.0% lower somatic/psychiatric intolerability discontinuation rate). Of note, the median durations of treatment for modafinil and pramipexole (9.4 and 7.0 months, respectively) provide some of the longest overall observation periods for bipolar disorder patients, published to date (Cassano et al., 2004; Nasr et al., 1995; El-Mallakh et al., 2010). Our patients, in general, had treatment resistant bipolar disorders, in that prior to augmentation with modafinil or pramipexole, they were already taking on average 3.5 prescription psychotropic medications, yet still had an average CGI-BP-OS above 4.
Effects of modafinil on emotional processing in first episode psychosis
2011, Biological PsychiatryCitation Excerpt :Modafinil also induces neurotransmitter changes in the hippocampus and limbic regions of the brain (23,33,35), which might explain its memory- and mood-enhancing properties. Modafinil has been used in several studies in healthy and mentally ill populations, and it has been associated with enhanced memory, inhibition control, mood, and symptoms related to depression in healthy (36–38), sleep deprived (39–43), narcoleptic (44–47), attention deficit and hyperactivity disorder (48,49), and depressive patients (50–52). Research in chronic, stable schizophrenia showed that modafinil improved some aspects of their cognitive deficits, such as attention, memory, fluency, and executive function (53,54).