Amitriptyline/perphenazine

Amitriptyline/perphenazine

Combination of
Amitriptyline	Tricyclic antidepressant
Perphenazine	Typical antipsychotic
Clinical data
Trade names	Duo-Vil, Etrafon, Triavil, Triptafen
AHFS/Drugs.com
Licence data	US Daily Med:link
Pregnancy category	US: D (Evidence of risk)
Legal status	US: ℞-only
Routes of administration	Oral
Identifiers
CAS Number	8015-22-3

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:

• Moderate-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 include

• Sedation
• Hypertension — high blood pressure.
• 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 — hair loss
• Photophobia
• Pigmentation
• Eczema up to exfoliative dermatitis
• Urticaria
• Erythema
• Itching
• Photosensitivity (increased sensitivity of affected skin to sunlight)
• Hypersalivation — excessive salivation.
• Hyperprolactinaemia — elevated blood prolactin levels. This may present with the following symptoms:

- Galactorrhea — the release of milk that is not associated with pregnancy of breastfeeding

- Gynaecomastia — the development of breast tissue in males

- Disturbances in menstrual cycle

- Sexual dysfunction

• Pigmentation of the cornea and lens
• Hyperglycaemia — elevated blood glucose (sugar) levels.
• Hypoglycaemia — low blood glucose (sugar) levels.
• 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 — elevated body temperature

- Autonomic instability (e.g. tachycardia, high blood pressure, diaphoresis, diarrhoea, etc.)

• Urinary retention — the inability to pass urine despite having urine to pass.
• 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 [the cells of the immune system that specifically destroy bacteria] count), thrombocytopaenia (a dangerous drop in platelet [a cell found in the blood that plays a crucial role in the blood clotting process] counts), purpura (the appearance of red or purple discolourations of the skin that do not blanch when pressure is applied), eosinophilia (raised eosinophil [the cells of the immune system that specifically fights off parasites] count)
• Hepatitis — inflammation of the liver
• Jaundice
• Pigmentary retinopathy
• Anaphylactoid reactions
• Oedema — the abnormal buildup of fluids in the tissues
• Asthma
• Coma
• Seizures
• Confusional states
• Disorientation
• Incoordination
• Ataxia
• Tremors
• Peripheral neuropathy — nerve damage
• Numbness, tingling and paresthesias of the extremities
• Dysarthria
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Tinnitus — falsely hearing ringing in the ears.
• Alteration in EEG patterns
• Paralytic ileus — cessation of the peristaltic waves that propel partially digested food through the digestive tract.
• Hyperpyrexia (elevated body temperature)
• Disturbance of accommodation
• Increased intraocular pressure
• Mydriasis

Pharmacology

Binding affinities (K_i[nM]; for human cloned receptors when available)

Macromolecule	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