From the FDA Drug Label
Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression
Imipramine would be best for adults aged 65 and older or adults beyond age 24 in the setting of depression, as the risk of suicidality is reduced in these age groups compared to placebo.
- Key considerations for prescribing imipramine include:
- Monitoring patients for clinical worsening, suicidality, and unusual changes in behavior
- Screening patients for bipolar disorder before initiating treatment
- Using extreme caution in patients with cardiovascular disease, increased intraocular pressure, or a history of seizure disorder 1
From the Research
Imipramine would be best for patients with chronic depression, particularly those with moderate to severe symptoms, as it has been shown to produce significant improvements in depressive symptoms, global severity of illness, and self-rated social and vocational function 2.
Key Considerations
- Imipramine is a tricyclic antidepressant that works by inhibiting the reuptake of serotonin and norepinephrine, with stronger effects on norepinephrine, which explains its effectiveness for certain symptom clusters.
- It is particularly useful for patients who haven't responded to first-line treatments like SSRIs or SNRIs, though it's not typically a first choice due to its side effect profile.
- Caution is warranted in patients with cardiovascular disease, glaucoma, urinary retention, or seizure disorders, and it should be avoided in patients at risk for suicide due to its lethality in overdose.
Dosage and Administration
- Imipramine is typically started at 25-50 mg at bedtime, gradually increasing to an effective dose of 150-300 mg daily, with blood level monitoring recommended at higher doses.
Side Effects and Tolerability
- Patients should be informed about common side effects including dry mouth, constipation, urinary retention, blurred vision, and orthostatic hypotension, which often improve with time.
- The safety profile of imipramine is generally less favorable compared to SSRIs, with a higher risk of adverse effects and lethality in overdose 3.
Comparison to Other Antidepressants
- A systematic review and meta-analysis of head-to-head trials found no significant difference in efficacy between tricyclic antidepressants, including imipramine, and SSRIs for the treatment of acute major depression 4.
- However, imipramine may be more effective for certain symptom clusters, such as sleep disturbances and neuropathic pain, due to its unique mechanism of action.