Successful use of modafinil in treatment-resistant bipolar depression in an elderly woman

Sir,

Treatment of bipolar depression in the elderly is challenging due to the presence of medical comorbidities and it is often resistant to treatment.[1] Modafinil with its novel mechanism of action, utilizing multiple neurotransmitter systems such as dopamine, hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate, is a well-tolerated medication with minimum drug interactions.[2] Lately, studies evaluating the role of modafinil in the treatment of bipolar depression in the adult population have shown encouraging results.[3] However, its use in treatment of depression in elderly is yet to be explored. In this context we present the first case report of successful use of modafinil in an elderly woman with resistant bipolar depression.

Mrs. A, a 61-year-old homemaker, presented to us with 30-year-long episodic illness with around 15 depressive and 3 hypomanic episodes and poor interepisodic functioning. She had received adequate trials of various combinations of mood stabilizers (lithium, valproate, and lamotrigine) and antidepressants (amitryptiline, imipramine, clomipramine, fluoxetine, fluvoxamine, paroxetine, escitalopram, pregabalin, prothiaden, venlafaxine, and reboxitin) and quetiapine with only partial improvement. She had never attained premorbid levels of functioning. For the past eight months, she had worsening of her symptoms-pervasive sad mood, crying spells, anhedonia, easy fatigability, decreased sleep and appetite, and features suggestive of apathy. She had history of hypertension and hypothyroidism for four years and was on treatment for the same. There was family history of hypothyroidism in two children. On physical examination she was overweight (BMI=26.6 kg/m²). Her blood pressure was controlled (116/82 mmHg) on a combination of losartan 50 mg/day and hydrochlorthiazide 12.5 mg/day. On mental status examination, she had psychomotor retardation, depressive cognitions, death wishes, depressed effect with impaired attention, and difficulty in new learning. She scored 31 on the Hamilton depression rating scale (HDRS) and 61 on the apathy evaluation scale.[4] Her thyroid function tests and serum vitamin B12 levels were normal. Magnetic resonance imaging revealed generalized atrophy predominantly temporal with leukoaraiosis. Atherosclerotic changes were noted in bilateral internal carotid arteries. In view of the above, she was diagnosed as having bipolar II disorder without full interepisodic recovery, current episode moderate depression. She was then started on modafinil, titrated to 50 mg/day. She has shown gradual improvement with the same and has reached premorbid levels of functioning. When last followed up, at the end of 16 weeks, she had a score of 8 on the HDRS and 31 on the apathy evaluation scale.

The index patient had resistant bipolar depression with significant apathy which improved significantly after modafinil was started. Modafinil with its apparent two-pronged action on both depressive and apathetic symptoms, and lack of serious side effects,[3] is an important therapeutic option in this, otherwise difficult to treat, population. Indirect evidence implicates the dopaminergic system in the pathogenesis of apathy, and modafinil through its dopaminergic action is reported to be successful in treatment of apathy.[5] However, further systematic trials are needed to elucidate the mechanism of modafinil's antidepressant and antiapathy actions.