Amitriptyline/perphenazine (Duo-Vil, Etrafon, Triavil, Triptafen) is a formulation that contains the tricyclic antidepressant amitriptyline and the medium-potency typical (first-generation) antipsychotic, perphenazine. In the United States amitriptyline/perphenazine is marketed by Mylan Pharmaceuticals Inc. and Remedy Repack Inc.

Medical uses In the United States amitriptyline/perphenazine is indicated for the treatment of patients with:amitriptyline/perphenazine (Rx) - Etrafon, Triptafen, Triavil [Internet]. Medscape Reference. [cited 2013 Oct 7]. Available from: http://reference.medscape.com/drug/etrafon-triptafen-amitriptyline-perphenazine-342946 Moderate to severe anxiety and/or agitation and depression Depression and anxiety in association with chronic physical disease Schizophrenia with prominent depressive symptoms

Adverse effects Common (>1% incidence) adverse effects includeTruven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 7]. Greenwood Village, CO: Thomsen Healthcare; 2013. Sedation Hypertension Neurological impairments (such as extrapyramidal side effects which include dystonia, akathisia, parkinsonism, muscle rigidity, etc.) Anticholinergic side effects such as: Blurred vision Constipation Dry mouth Nasal congestion Increased appetite Weight gain Nausea Dizziness Headache Vomiting

Unknown frequency adverse effects include Diarrhoea Alopecia Photophobia Pigmentation Eczema up to exfoliative dermatitis Urticaria Erythema Itching Photosensitivity Hypersalivation Hyperprolactinaemia — This may present with the following symptoms: Galactorrhea Gynaecomastia Disturbances in menstrual cycle Sexual dysfunction Pigmentation of the cornea and lens Hyperglycaemia Hypoglycaemia Disturbed concentration Excitement Anxiety Insomnia Restlessness Nightmares Weakness Fatigue Diaphoresis — excessive/abnormal sweating.

Uncommon/Rare adverse effects include Tardive dyskinesia, an often irreversible adverse effect that usually results from chronic use antipsychotic medications, especially the high-potency first-generation antipsychotics. It is characterised by slow (hence tardive), involuntary, repetitive, purposeless muscle movements. Neuroleptic malignant syndrome, a potentially fatal complication of antipsychotic drug use. It is characterised by the following symptoms: Muscle rigidity Tremors Mental status change (e.g., hallucinations, agitation, stupor, confusion, etc.) Hyperthermia Autonomic instability (e.g., tachycardia, high blood pressure, diaphoresis, diarrhoea, etc.) Urinary retention Blood dyscrasias, e.g., agranulocytosis (a potentially fatal drop in white blood cell count), leukopaenia (a drop in white blood cell counts but not to as extreme an extent as agranulocytosis), neutropaenia (a drop in neutrophil count), thrombocytopaenia (a dangerous drop in platelet counts), eosinophilia (raised eosinophil count), purpura (the appearance of red or purple discolourations of the skin that do not blanch when pressure is applied) Hepatitis Jaundice Pigmentary retinopathy Anaphylactoid reactions Oedema Asthma Coma Seizures Confusional states Disorientation Incoordination Ataxia Tremors Peripheral neuropathy Numbness, tingling and paresthesias of the extremities Dysarthria Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Tinnitus Alteration in EEG patterns Paralytic ileus Hyperpyrexia (elevated body temperature) Disturbance of accommodation Increased intraocular pressure Mydriasis

Pharmacology

Binding affinities (Ki [nM]; for human cloned receptors when available)National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 7]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: Molecular target Amitriptyline Nortriptyline (Amitriptyline's active metabolite) Perphenazine Notes SERT 3.13 16.5 ? It is this and its NET-inhibiting action is believed to give amitriptyline its antidepressant action. NET 22.4 4.37 ? See above. DAT 5380 3100 ? 5-HT1A 450 294 421 Binding for human brain receptors had to be substituted in amitriptyline (AMI) and nortriptyline's (NOR) cases 5-HT2A 4.3 5 5.6 Binding for cloned rat receptors had to be substituted for AMI & NOR. Binding to this receptor is believed to be what gives the newer (atypical) antipsychotics, clozapine, quetiapine, olanzapine, ziprasidone, risperidone, sertindole and zotepine their lower extrapyramidal side effect (EPS) liability. 5-HT2C 6.15 8.5 132 (Binding) As above. This action is believed to be partly responsible for the lower EPS liability of newer antipsychotics and also responsible for their higher weight gain liability compared to most typical antipsychotics. 5-HT6 103 148 17 Cloned rat receptor was substituted for NOR's binding. 5-HT7 114 ? 23 Cloned rat receptor was substituted for AMI. α1A 24 55 10 Human brain receptors were substituted for AMI and NOR. α2A 690 2030 810.5 As above. D2 1460 2570 0.16 As above. D3 206 ? 0.13 Human receptors (their source was undefined) had to be substituted for AMI. H1 1.1 15.1 8 This receptor is at least partly responsible for the sedating effects of these three drugs and hence this combination product. Possibly also partly responsible for their weight gain liability. M1 12.9 40 1500 This is the main receptor responsible for the anticholinergic side effects mentioned above. M3 25.9 50 1848 This receptor is believed to be partly responsible for the metabolic adverse effects of the atypical antipsychotics. σ 300 2000 31.5 All three values are for binding to the guinea pig brain receptors.

See also Flupentixol/melitracen Olanzapine/fluoxetine Tranylcypromine/trifluoperazine

References