Selegiline remarkably improved stage 5 treatment-resistant major depressive disorder: a case report
A 51-year-old man had been diagnosed with major depression 6 years prior to beginning selegiline treatment. During that time, he was treated with imipramine, a tricyclic antidepressant (TCA) (150 mg/day), and his symptoms remitted. However, although he continued medication for 4 years, his depression relapsed. Imipramine was thus replaced with milnacipran, a serotonin and noradrenalin reuptake inhibitor (150 mg/day) and then paroxetine, a selective serotonin reuptake inhibitor (40 mg/day), but those were ineffective, and he was later admitted to our hospital. Concurrent administration of amoxapine, a tetracyclic antidepressant (TeCA) (150 mg/day), lithium carbonate (800 mg/day), and cabergoline (1 mg/kg) improved his symptoms, and he was discharged. His plasma lithium concentration was 0.61 mEq/L. However, he again relapsed into depression 8 months later, despite receiving treatment. His major symptoms included fatigue, loss of motivation, and decline in work efficacy. Subsequently, he was readmitted to our hospital.\nDuring this second hospitalization, amoxapine (200 mg/day), amitriptyline, a TCA (200 mg/day), imip-ramine (250 mg/day), and clomipramine, a TCA (150 mg/ day) were consecutively used for at least 4 weeks, but none were effective. Additional lithium augmentation had no effect, and the addition of olanzapine (5 mg/day) was ineffective. Likewise, pramipexole (2.625 mg/day) induced the side effects of oral dyskinesia and auditory hyperesthesia, while the addition of triiodothyronine was stopped because of palpitations. ECT was administered ten times, and depressive symptoms disappeared transiently. However, the patient’s depression relapsed again 1.5 months later, despite the continuation of clomipramine after ECT. Selegiline (2.5 mg/day) treatment was started after he signed the informed consent form. The daily dose of selegiline was increased by 2.5 mg every week up to a maximum of 10 mg/day. Mianserin, a TeCA, (60 mg/day), and valproate (600 mg/day) were also concurrently used, but the dosages of those drugs remained constant during selegiline treatment. Before initiating selegiline treatment, the patient received a score of 19 on the 17-item Hamilton Depression Rating Scale (HDRS). During selegiline treatment, his score on the HDRS decreased to 9 points at week 8 and 4 points at week 20. He returned to work after 49 weeks of selegiline treatment. No side effects from selegiline treatment were either observed or reported. We followed up with the patient approximately 2 years and 5 months after the trial with selegiline. During this period, no relapse occurred.\nFDG-PET scans were measured twice, before selegi-line treatment and after 20 weeks of selegiline treatment. Two experienced nuclear medicine physicians visually interpreted the images. Twenty weeks after selegiline treatment, selegiline-induced enhancement of glucose metabolism was observed in the bilateral basal ganglia by FDG-PET, while decreases were shown in those in the occipital lobe (). The methods used to conduct and analyze the PET scan were as follows: a 10-minute regional static scan was performed with a Siemens ECAT HR+ scanner using the three-dimensional (3D) mode, and the image was reconstructed in the brain mode, using Siemens’ ecat software, version 7.2.2 (Siemens AG, Munich, Germany). The images were acquired via 3 minutes of transmission scanning and 10 minutes of emission scanning. The energy window was 350−650 keV. In the brain mode, the acquired 3D sonograms were converted into two-dimensional (2D) sonograms, using Fourier rebinning. The images were reconstructed using the direct inversion Fourier transformation method. We used a Hanning reconstruction filter with a 4 mm full width at half-maximum (FWHM). The reconstruction matrix was 256 × 256, and the field of view was 33 cm in diameter. The FWHM was 6.4 mm after reconstruction.\nMoreover, the patient’s plasma dopamine levels (<5 to 9 pg/mL) and urine PEA levels (<0.5 to 179.4 ng/mg CRE [creatinine]) were greater after 12 weeks of selegiline treatment compared with baseline, although the plasma HVA and noradrenalin levels were not changed. The MAO-B activity of blood platelets was nearly completely inhibited by administering selegiline 10 mg/day.