Duloxetine-Induced Subcortical Growth in a Patient With Major Depressive Disorder and Panic Disorder

Mr. H is a 38-year-old male patient with a single MDD-with-PD episode for 1 year (Hamilton Rating Scale for Depression [Ham-D]): 43; Panic Disorder Severity Scale [PDSS]: 27). He received the following antidepressant therapy: fluoxetine, venlafaxine, escitalopram, and mirtazapine each for 3–4 months without much improvement (Ham-D lowest score: 35; PDSS lowest score: 23). Because of nonresponse to previous antidepressants, he started to receive duloxetine 30 mg initially with abrupt switching from mirtazapine 60 mg/day (Ham-D: 41; PDSS: 25), and was titrated to 60 mg within 2 weeks without any significant side effects except mild nausea and sedation. After 6 weeks of therapy, his MDD and PD symptoms improved (Ham-D: 20; PDSS: 11). Structural brain MRI scans were obtained with a 3T GE version scanner. Scans with three-dimensional fast spoiled gradient-echo recovery (3D-FSPGR) T1W1 (TR=11.2 msec, TE=5.2 msec, matrix=256 x 256, field of view=260 mm, number of excitation=1, slice thickness=1 mm, 180 slices; no gap) were performed at first visit and 6th-week visit. Structural MRI was processed with FMRIB's Integrated Registration and Segmentation Tool function (FIRST Version 1.2) of FSL (FMRIB Software Library; Version 4.1.1; Oxford, England) to perform subcortical brain segmentation using a shape and appearance model. The volume changes are listed as follows (Table 1).

Sheline has proposed a theory of a limbic-cortical-striatal-pallidal-thalamic circuit (including putamen) in MDD pathogenesis. MDD patients seemed to “over-recruit” a memory system sensitive to negative stimuli, which also includes caudate-putamen areas. They had increased linear-increase activities of putamen with other limbic structures to sad faces.¹ PD patients had reduced putamen activation while performing a nondominant hand-motor task, and putamen dysfunction might play a role in PD.² A comprehensive meta-analysis showed moderate putamen volume reduction in MDD patients.³ Yoo et al.⁴ reported that PD patients had gray-matter volume decrease, and the reduction severity might be correlated with PD symptom severity. Duloxetine might improve the symptoms of MDD and PD through the growth effects in the putamen. Gorman et al.⁵ proposed a neuroanatomical “fear network” with projections to the brainstem in PD. This system provides an explanation of conditioned fear response.⁵ Serotonin transporter binding abnormalities in the brainstem were also observed in MDD patients. This patient's brainstem regeneration after duloxetine treatment might be related to serotonin-reuptake inhibition and serotonin level elevation at the brainstem. From the above findings, a possible role serotonin and norepinephrine reuptake-inhibition could explain “subcortical growth” with duloxetine in this patient with MDD and PD.

I thank Dr. Yuan-Yu Hsu (Department of Medical Imaging, Buddhist Tzu-Chi General Hospital Taipei Branch) for MRI acquisition help and technique assistance.