From the FDA Drug Label
For most patients with illness of mild to moderate severity, a starting daily dose of 75 mg is recommended. Dosage may subsequently be increased or decreased at appropriate intervals and according to individual response. The usual optimum dose range is 75 mg/day to 150 mg/day In more severely ill patients higher doses may be required with subsequent gradual increase to 300 mg/day if necessary. Additional therapeutic effect is rarely to be obtained by exceeding a dose of 300 mg/day. The maximum dose for dothiepin for depression with anxiety is 300 mg/day. This dose may be necessary for more severely ill patients, but it is rarely necessary to exceed this dose to obtain additional therapeutic effect 1.
From the Research
The maximum dose of dothiepin for depression with anxiety is 225 mg per day, as indicated by the most recent and highest quality study available 2.
Key Considerations
- Typically, treatment begins with a lower dose of 75 mg daily, often taken as a single dose at bedtime, which can be gradually increased as needed.
- For most patients, an effective dose range is between 75-150 mg daily.
- The maximum dose should only be used in severe cases and under close medical supervision due to dothiepin's significant side effect profile.
Mechanism and Safety
- Dothiepin is a tricyclic antidepressant that works by increasing levels of serotonin and norepinephrine in the brain, which helps improve mood and reduce anxiety.
- However, it carries risks of cardiotoxicity at higher doses and has a narrow therapeutic window, meaning the gap between effective and toxic doses is relatively small.
- Due to these safety concerns, dothiepin is typically not a first-line treatment for depression and anxiety in current practice, with many clinicians preferring newer antidepressants with better safety profiles such as SSRIs or SNRIs.
Clinical Evidence
- A study from 1997 compared the safety and antidepressant efficacy of venlafaxine and dothiepin in geriatric patients with major depression, finding that both treatments were effective but with different side effect profiles 2.
- Earlier studies also supported the efficacy of dothiepin in treating depression with anxiety, with dose ranges of 75-200 mg/day being commonly cited 3, 4, 5, 6.