Long-Term Risks and Benefits of Low-Dose Lithium for Treatment-Resistant Depression with Nortriptyline

Definition of Treatment-Resistant Depression (TRD)

Treatment-resistant depression is most commonly defined as depression that has failed to respond to at least two adequate trials of antidepressants with different mechanisms of action, as defined by the American Psychiatric Association 1, 2
An adequate antidepressant trial requires a minimum effective dosage and administration for at least 4 weeks, with confirmation of adequate dose and duration, according to the National Institute of Mental Health 2, 3

The American Academy of Family Physicians recommends nortriptyline dosing of 10 mg at bedtime initially, with a maximum of 40 mg per day, for patients with treatment-resistant depression 4
Nortriptyline tends to be sedating and may be useful in patients with agitated depression and insomnia, as noted by the American Family Physician 4
The therapeutic blood level "window" of 50-150 ng/mL should be monitored for patients taking nortriptyline, according to the American Family Physician 4

The American Psychiatric Association confirms that treatment-resistant depression diagnosis requires at least two failed adequate trials of antidepressants with different mechanisms of action 1, 2
The National Institute of Mental Health recommends ensuring each trial was at minimum effective dose for at least 4 weeks 2
The American Academy of Family Physicians suggests starting with 10 mg of nortriptyline at bedtime and titrating up to a maximum of 40 mg per day, with monitoring of therapeutic blood levels 4