Effectiveness of methylphenidate as augmentation therapy after failure of adjunctive neuromodulation for patients with treatment-refractory bipolar depression: a case report
Mr U, a 56-year-old man with bipolar I disorder according to DSM-Fifth Edition criteria, experienced his first melancholic depression in 1976, which was followed by five melancholic episodes and four manic episodes. He did not show any comorbid psychiatric condition and had no history of drug or alcohol abuse.\nHis sixth melancholic depressive episode began in March 2008, just after a prison guard workmate had committed suicide. Mr U was admitted to our bipolar department on April 1, 2008. He showed a depressed and anxious mood, negative and obsessive thinking, loss of interest in activities, impairment in activities of daily living, psychomotor retardation, self-blaming behavior, guilty and suicidal thoughts, insomnia, reduced appetite, and a 5 kg loss of body weight. His laboratory examinations included a full blood count, blood biochemistry and urinalysis, electrocardiography, electroencephalography, and structural cerebral magnetic resonance imaging. His physical and laboratory examinations were normal. From April 1, 2008, blood pressure, pulse and temperature were monitored once daily by a nurse. His initial 21-item Hamilton Depression Rating Scale score was 37 and his Clinical Global Impression-Severity score was 6. From April 1, 2008 until June 10, 2010, he received various antidepressant (venlafaxine extended- release, clomipramine or duloxetine, combined with either paroxetine or mirtazapine) and mood stabilizer (olanzapine, aripiprazole, or sodium valproate) combinations with no significant clinical improvement. Each medication was prescribed at an optimum and stable dosage for the minimum recommended duration, with no significant clinical improvement. On February 6, 2009, we assessed the patient’s whole-brain voxel-based regional cerebral blood flow with 99mTc-ethyl cysteinate dimer single photon emission computed tomography, and hypoperfusion was shown in the bilateral anterior cingulate cortices, the right inferior parietal cortex, and the left dorsolateral and bilateral orbital prefrontal cortices. rTMS was initiated on February 15, 2009. Twenty treatment sessions were administered over a 4-week period (five sessions per week). In mid March, after these sessions were completed, Mr U showed no significant clinical improvement. rTMS was initiated again, with 20 treatment sessions being administered over a 4-week period until April 15, 2009. After the last rTMS session, Mr U showed no significant clinical improvement. His physicians initiated electroconvulsive therapy three times a week on April 18, 2009 for 2 months until June 19, 2009. Mr U showed no significant clinical improvement after 24 sessions of electroconvulsive therapy. At that time, he was treated with a combination of fluoxetine 80 mg/day, duloxetine 360 mg/day, mirtazapine 60 mg/day, and sodium valproate 1,000 mg/day. On June 29, 2009, we added methylphenidate at a dose of 10 mg/day for one week. Two days after introduction of methylphenidate, Mr U reported some mood improvement after a single early morning dose. The second week after its initiation, the dose of methylphenidate was increased to 20 mg/day for one week using an extended-release tablet formulation, with significant improvement. Two weeks later, Mr U achieved significant and lasting clinical improvement, with Hamilton Depression Rating Scale and Clinical Global Impression-Severity scores of 8 and 3, respectively. He was in a stable condition one month after starting adjunctive treatment with methylphenidate. He tolerated his medications well and did not report any side effects. His antidepressants and methylphenidate were gradually tapered and finally discontinued after one year. He remains well on sodium valproate monotherapy and is regularly followed up at our bipolar department.