Polyneuropathy of different etiologies is often associated with pain and the standard treatment for this type of pain is gabapentinoids or antidepressants. The hypothesis of this study is that the combination of the gabapentinoid pregabalin and the antidepressant imipramine will provide better pain relief than the single compounds alone.

This is a randomized, placebo-controlled, double-blind, 4-way, cross-over trial of pregabalin 300 mg/day, imipramine 75 mg/day and their combination versus placebo. The study will include 60 patients and the treatment outcome will be pain intensity as measured by numeric rating scales.

Inclusion Criteria:

• Age between 20 - 85 years.
• Characteristic symptoms of polyneuropathy for at least 6 months.
• Polyneuropathy diagnosis confirmed by typical clinical signs (distal sensory disturbance/lack of distal deep tendon reflexes) and/or electrophysiological tests and/or abnormal quantitative sensory tests.
• Total pain intensity rating of at least 4 on a 0-10 points numeric rating scale.
• Pain present at least 4 days a week.
• For diabetics: diabetes diagnosis for at least 6 months and stable metabolic control for at least 3 months.
• For other secondary polyneuropathies: stable for at least 6 months.
• For fertile females: adequate anticonceptive treatment.
• Written informed consent.

Exclusion Criteria:

• Other cause of pain.
• Contraindications against imipramine.
• Allergic reactions towards imipramine or pregabalin.
• Known adverse reactions during imipramine or pregabalin treatment.
• Pregnancy.
• Severe systemic disease.
• Ongoing treatment with antidepressants, antipsychotics, anticonvulsants, opioids, propranolol, kinidine, monoamine oxidase inhibitor.
• Inability to follow study protocol.