[11.] Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dudner R Effects of desipramine
, amitriptyline, and fluoxetine on pain in diabetic neuropathy.
The first study, involving 26 subjects who completed a trial of doxepin or desipramine
, reported a trend toward a significant relation between changes in pain and depression (r = .26, P = .099).
In the same intent-to-treat analysis, a separate group of 135 women who received desipramine
did not improve significantly more than 66 women who received placebo in the double-blind part of the trial.
Table 1 Tricyclic antidepressants used to treat pain Drug Dosage range for Comments pain (off-label) Amitriptyline 10 to 100 mg/d High sedation, high anticholinergic side effects Amoxapine 50 to 100 mg/d Low sedation, moderate anticholinergic side effects Clomipramine 25 to 100 mg/d Low sedation, low anticholinergic side effects Desipramine
25 to 100 mg/d Low sedation, low anticholinergic side effects Imipramine 25 to 100 mg/d Moderate sedation, moderate anticholinergic side effects Nortriptyline 10 to 75 mg/d Moderate sedation, low anticholinergic side effects Source: Reference 8 SNRIs
* The FDA warns against using desipramine
in patients with cardiovascular disease; fluoxetine and other CYP2C19 inhibitors may reduce the efficacy of clopidogrel.
After the 8-week study, 55 outpatients at a mean age of 41.7 years who failed to respond were enrolled in a 4-week, double-blind trial and given either a fluoxetine dose increase, lithium augmentation of fluoxetine, or desipramine
augmentation of fluoxetine.
If neither methylphenidate nor an amphetamine is effective, the next class of drugs to try is a tricyclic antidepressant, such as desipramine
Typically, therapeutic doses of antidepressants with anti-histaminergic properties, such as doxepin at antidepressant doses, amitriptyline, or desipramine
, do not selectively block H1 receptors, but act at cholinergic, serotonergic, adrenergic, histaminergic, and muscarinic receptors, which can cause adverse effects.
There were no reports of eye anomalies associated with exposure to desipramine
, fluvoxamine (Luvox), or venlafaxine (Effexor).
Eight randomized, studies with efficacy data from 1,959 inpatients and outpatients with major depressive disorder found that reboxetine compared favorably with desipramine
, imipramine, fluoxetine, and placebo, which led to its approval in other countries.
To help affected patients settle down and sleep, a tricyclic antidepressant such as desipramine
is useful even in nondepressed patients.
The selective norepinephrine reuptake inhibitor reboxetine is used in Europe, but not in the United States, for both monotherapy and augmentation in depression, and such well-established antidepressants as venlafaxine and the tricyclic desipramine
appear to enhance synaptic norepinephrine along with serotonin activity.