There is considerable variation in the comparative types and effectiveness of antidepressants on specific conditions. These variations are detailed under specific conditions.
All classes of antidepressants are associated with withdrawal syndromes253–256 and should be tapered slowly if the drug is discontinued. Antidepressant abuse and misuse have also been reported, but are rare. Most reported cases of antidepressant abuse occur in individuals with comorbid substance use and mood disorders.
There is no significant difference between tricyclic antidepressants (TCAs) and placebo in pain relief for patients with chronic low back pain.257,258
While TCAs are considered first-line and second-line therapies in neuropathic pain treatment,96,167,259–262 guideline recommendations differ and supportive data are of varied quality. Older analyses and guidelines, and those before the definition of neuropathic pain changed in 2011, appear more supportive.
More recent analyses report very modest efficacy compared to other antidepressants and anticonvulsants263 and suggest that the evidence base for TCAs in neuropathic pain is weak, due to the small magnitude of clinically meaningful effects and the high risk of bias in the RCTs.100,247,248,264,265 Large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes.96
Neuropathic pain associated with cancer or human immunodeficiency virus (HIV) appears refractory to TCAs.
There is also support for some analgesic combinations in selected neuropathic pain conditions.94
In fibromyalgia, the most effective TCA appears to be amitriptyline (number needed to treat [NNT] 4.9).249,266
Amitriptyline probably provides very good pain relief to some patients with neuropathic pain or fibromyalgia, but in a minority; amitriptyline will not work for most people. When initiating a therapeutic trial, start at the lowest recommended dose (eg amitriptyline 5–10 mg at night) and assess the patient for benefit and harm at one week.100 If needed, increase the dose slowly to minimise adverse effects; the maximum dose is approximately 75–100 mg at night.
In older patients, TCAs should be used with caution. Medications with anticholinergic activity increases risk of cognitive impairment, risk of falls and even mortality.267,268
Serotonin noradrenaline reuptake inhibitors
Duloxetine is a recommended treatment in updated guidelines for osteoarthritis.269 It is as effective as other first-line treatments (eg NSAIDs) for pain and disability of osteoarthritis.270,271 Duloxetine appears to be well tolerated in older patients with osteoarthritis pain (of the knee).270
There is evidence that some antidepressants, in particular duloxetine and venlafaxine, may be effective first-line treatments for neuropathic pain, including diabetic polyneuropathy.96,255,256,263 Duloxetine has been shown to be effective and safe for the treatment of painful diabetic peripheral neuropathy in older patients.272
Chemotherapy-induced peripheral neuropathy (CIPN) is poorly understood and is resistant to treatment. However, duloxetine (30 mg titrated to 60 mg/day over five weeks) has resulted in a modest reduction in pain severity relative to placebo.273 Additional benefits included reduced numbness and tingling of the feet, and improved quality of life.273
The serotonin noradrenaline reuptake inhibitor (SNRI) duloxetine is effective in reducing pain and improving quality of life in fibromyalgia.249,274 The NNT is approximately six.256,275 However, it is not effective at improving sleep or fatigue.274
SNRIs are regarded as a first-line therapy for managing neuropathic pain.96 The NNT is approximately seven for 50% pain relief.96 When initiating a therapeutic trial, start at the lowest recommended dose (eg duloxetine 30 mg) and assess the patient for benefit and harm at one week. If insufficient but partial pain relief is achieved, increase the dose and reassess within one week; this may be repeated. Modest reduction in pain severity may be achieved with duloxetine dose titrated to 60 mg/day over five weeks. Duloxetine 60–120 mg/day provides analgesia for diabetic neuropathy, with lower efficacy for fibromyalgia.
Use the lowest individualised effective dose to minimise adverse effects, the most common of which is intolerable drowsiness. If the benefit–harm ratio is unacceptable, consider stopping the drug.
Selective serotonin reuptake inhibitors
There is only limited evidence for the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in neuropathic pain.262