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Modafinil as an Alternative to Methylphenidate as Augmentation for Depression Treatment

TO THE EDITOR: Psychostimulants are occasionally employed as an augmentation strategy to traditional antidepressants, despite a lack of adequate randomized, placebo-controlled studies. They are particularly useful in the treatment of depressed, severely medical ill patients when either traditional antidepressants have failed to achieve response after adequate duration and dosage or when there is a critical need for rapid resolution of depressive symptoms. Modafinil, a novel wakefulness-promoting agent that is approved by the Food and Drug Administration for narcolepsy, has been reported to be effective for the augmentation of antidepressants in psychiatric outpatients with major depression,^1,2 in a series of five medically ill patients,³ and as monotherapy for poststroke depression.⁴ We report here on a patient with remarkable response to modafinil.

Case Report

Mr. A was a 78-year-old man with a history of myocardial infarction resulting in four-vessel coronary artery bypass surgery, ischemic cardiomyopathy, and nonsustained ventricular tachycardia following mitral valve replacement surgery who was admitted for progressive dyspnea and fatigue. He was admitted to the cardiology service and was subsequently found to have a non-ST elevated myocardial infarction. The infarction was medically managed. His hospital course was complicated by respiratory failure from aspiration pneumonia, which required mechanical ventilation and vasopressor support. A further workup revealed that he had a paraesophageal hernia with associated gastric necrosis. He underwent an exploratory laparotomy and was treated with hernia reduction and total gastrectomy, tracheostomy, and percutaneous gastrojejunostomy placement. After a protracted hospital course of nearly 60 days, he was transferred from the intensive care unit to a pulmonary step-down unit.

Mr. A had already been taking fluoxetine, 30 mg/day, for the treatment of depression for more than 4 weeks before he was transferred to the pulmonary service. His apathy, tearful affect, and depressed mood had continued. He would intermittently decline to participate in physical, respiratory, and speech therapy. His refusals were interfering with his rehabilitation and an attempt to wean him from his mechanical ventilator. The team decided to initiate methylphenidate therapy and began cardiac monitoring at the same time, given Mr. A’s multiple cardiac risk factors and history of nonsustained ventricular tachycardia. Methylphenidate was titrated to 5 mg b.i.d. Mr. A responded well to methylphenidate and began to interact more meaningfully with his wife and health care providers. After 3 or 4 days, he demonstrated significant improvement in his affect and started to participate in physical therapy as well as to speak using his Passey-Muir valve. Unfortunately, cardiac monitoring noted beat runs of an asymptomatic nonsustained ventricular tachycardia lasting 8–30 beats between days 4 and 5. The psychiatric consultation service was asked for an alternative to methylphenidate. Mr. A was given modafinil, 50 mg/day, and finally titrated to 200 mg/day by day 3. He tolerated this well and demonstrated improvements in his affect and ability to participate in rehabilitation. After 2 weeks, he was weaned off of the mechanical ventilator and discharged to an acute inpatient rehabilitation facility.

Discussion

This report highlights the effectiveness of modafinil as an alternative to methylphenidate, especially in a patient with significant cardiac comorbidity. Although quality data in this challenging population are limited, the clinician is frequently faced with the need to obtain rapid resolution of depression that may prove fatal in the severely medically ill patient. Modafinil ultimately proved to be effective for Mr. A. Electroconvulsive therapy is another treatment consideration, although it is more costly and frequently unavailable outside of tertiary care hospitals.⁵ The efficacy of modafinil for the augmentation of depression treatments and in severely medically ill patients remains to be replicated in randomized, controlled studies. There is need for such trials in this challenging population.

The mechanism of action for modafinil remains unclear. It has been postulated that modafinil acts as a central -adrenergic agonist, that it decreases the activity of -aminobutyric acid, and increases glutamate transmission in the cortex, hypothalamus, and striatum.⁶ Also, depression is often difficult to clinically distinguish from fatigue secondary to underlying medical illness. It is plausible that the wakefulness-promoting properties of modafinil are the main action that enables patients to participate more meaningfully in their recovery. Modafinil has potential drug-drug interactions, including the induction of CYP 3A4 (with autoinduction through this pathway) and the inhibition of CYP 2C19 and CYP 2C9. Although modafinil generally lacks peripheral vasopressor and cardiac side effects, dyspnea, palpitations, angina, and transient ischemic T-wave changes have been reported in patients with left ventricular hypertrophy or mitral valve prolapse.⁶

REFERENCES

1. Menza MA, Kaufman KR, Castellanos AM: Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry 2000; 61:378–381[Medline]
2. DeBattista C, Lembke A, Solvason BH, Ghebremichael R, Poirier J: A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol 2004; 24:87–90[CrossRef][Medline]
3. Schwartz TL, Leso L, Beale M, Ahmed R, Naprawa S: Modafinil in the treatment of depression with severe comorbid medical illness. Psychosomatics 2002; 43:336–337[Free Full Text]
4. Sugden SG, Bourgeois JA: Modafinil monotherapy in poststroke depression. Psychosomatics 2004; 45:80–81[Free Full Text]
5. Christopher EJ: Electroconvulsive therapy in the medically ill. Curr Psychiatry Reports 2003; 5:225–230
6. Cox JM, Pappagallo M: Modafinil: a gift to pormanteau. Am J Hosp Palliat Care 2001; 18:408–410[Abstract/Free Full Text]

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Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Xiong, G. L. Articles by Goebel, J. Search for Related Content PubMed Citation Articles by Xiong, G. L. Articles by Goebel, J. Geriatric Psychiatry Hospitals, Hospital Treatment Depression Other Somatic Therapy

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