Dothiepin (Dosulepin) Hydrochloride 75 mg Once Daily for Depression
Dothiepin 75 mg once daily is an appropriate and well-established dosing regimen for treating depression in adults, with this single daily dose demonstrating equivalent efficacy to divided dosing while potentially offering better tolerability and improved compliance. 1
Dosing Strategy and Rationale
The 75 mg once-daily dose represents the standard therapeutic starting point, with 75% of patients in long-term studies requiring between 125-150 mg/day for optimal response, though many respond adequately to 75 mg. 2
Single daily dosing at bedtime is preferable to divided doses because it provides better control of insomnia symptoms during early treatment while maintaining therapeutic efficacy comparable to three-times-daily regimens. 1
Dose titration should occur in increments of the initial dose every 5-7 days until therapeutic benefits become apparent or significant side effects emerge, with a full therapeutic trial requiring 4-8 weeks before judging efficacy. 3
The therapeutic range extends from 75-225 mg/day, allowing for upward titration if the initial 75 mg dose proves insufficient after an adequate trial period. 2
Expected Clinical Outcomes
Dothiepin demonstrates particular efficacy in anxious depression, reducing both depressive symptoms and associated anxiety, which distinguishes it from some other tricyclic antidepressants. 4
Response rates are favorable, with only 11.8% of patients failing to respond in long-term studies, though approximately 19.6% may require therapy exceeding 2 years for chronic depressive states. 2
After 9 months of treatment, 75% of successfully treated patients can discontinue therapy, though reassessment through dose reduction should occur after this period to determine ongoing need. 3, 2
Safety Profile and Monitoring
Dothiepin may cause fewer intolerable side effects and less cardiotoxicity than other tricyclic antidepressants, making it particularly suitable for elderly patients and those with underlying cardiac disease. 4
Common side effects include dry mouth (affecting 2.5% of patients) and drowsiness (affecting 1.7%), with only 9.7% of patients requiring withdrawal due to adverse effects in long-term studies. 2
The once-daily dosing regimen produces lower peak blood levels compared to divided dosing, which may contribute to improved tolerability while maintaining therapeutic efficacy throughout the 24-hour period. 1
Critical Clinical Considerations
Discontinuation must be gradual over 10-14 days to limit withdrawal symptoms when stopping therapy or during dose reduction for reassessment. 3
Patients with depression and psychosis require concomitant antipsychotic medication, as antidepressant monotherapy is insufficient for this presentation. 3
Bedtime administration is optimal because dothiepin's sedating properties can be leveraged therapeutically for patients with insomnia, a common feature of depression. 1
Special Populations
In elderly patients, dothiepin's favorable cardiac safety profile makes it preferable to other tricyclics, though standard precautions regarding anticholinergic effects and orthostatic hypotension still apply. 4
For patients with chronic depressive states or inadequate personalities, dothiepin has demonstrated particular utility, with some patients benefiting from maintenance therapy beyond 2 years. 2