Background circle Clinical depression has a major impact on individuals and society, often presenting the clinician with a significant challenge. Recent evidence suggests that synthetic antidepressants-although effective in the treatment of severe depressed mood-may have only a weak effect against mild-moderate forms of depression. In such cases, nonpharmaceutical options may be indicated. Furthermore, research findings suggest that select natural products are effective adjuvants when combined with synthetic antidepressants. Research concerning the treatment of depression emphasizes individual monotherapies, which is often incongruent with clinical reality. In practice, clinicians often use a variety of interventions; however, this approach may not be systematic, and many interventions used may not be based on strong evidence. Primary objective circle This article proposes an evidence-based prescriptive clinical model based on the biopsychosocial model to treat unipolar depression. The "Antidepressant-Lifestyle-Psychological-Social (ALPS) depression treatment model" integrates nonpharmacological interventions (such as complementary medicines, lifestyle advice, and psychosocial techniques) for use by clinicians. Results circle Initially a review of nonpharmacological mood-elevating interventions was undertaken. Evidentiary support was revealed for use of psychological techniques such as cognitive and behavioral medicine and interpersonal therapy, St John's wort, S-adenosylmethionine, and aerobic and anaerobic exercise. There were inconsistent research findings for acupuncture, omega-3 fish oils, and L-tryptophan for depressed mood. From these evidence-based interventions an integrative model was formed. Clinical recommendations in addition to a practical stepped-care decision tree are outlined. Conclusion circle The ALPS model has the potential to improve treatment outcomes and reduce relapse rates in clinical depression and warrants research using rigorous and appropriate methodology.