The long-term outcome of patients with addictive disorders is closely linked to the bio-psycho-social variables, the interactions between factors and, to psychiatric comorbidities.

Our case report is about a 28 years old male with an 8-years history of heroin dependence, and occasionally cocaine, ecstasy abuse.

4 years ago, he started a long-term Methadone maintenance treatment, and during this time he had several relapses and hospitalizations, most of them generated by recurrent major depressive episodes.

At his last admission in the detox clinic, transferred from the Emergency Hospital with a chronic amphetamine intoxication, minor ECG and EEG abnormalities, he had paranoid thoughts, delusional-hallucination behavior, ambivalence toward his mother, ideas of culpability, dysphoria, occasional suicidal thoughts, insomnia and fatigue, also opiates and amphetamines urine positive tests. At that moment he was under treatment with Methadone (75 mg/day ongoing) and Venlafaxine (stopped). He received an atypical antipsychotic as co-therapy (Quetiapine titrated up to 400 mg/day). After 3 weeks of hospitalization the symptomatology improved, with delusional thoughts and behavior remission.

In ambulatory, the patient was maintained on: Methadone 75 mg/day, Quetiapine 300 mg/day and received CBT, with a high compliance to pharmaco- and psychotherapy.

The patient outcome based on screening tests, CGI, MADRS and Quality of Life Scales proved the usefulness, efficiency and high tolerability of an atypical antipsychotic in the acute phase (psychotic-affective episode secondary to amphetamine intake) and also in long-term therapy for the prevention of drug and potentially addictive substances subsequent to depressive episodes along with Methadone.