Amitriptyline/perphenazine

Amitriptyline/perphenazine 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 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 adverse effects include:

Sedation
Hypertension
Neurological impairments
Anticholinergic side effects such as:
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:
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, involuntary, repetitive, purposeless muscle movements.
Neuroleptic malignant syndrome, a potentially fatal complication of antipsychotic drug use. It is characterised by the following symptoms:
Urinary retention
Blood dyscrasias, e.g., agranulocytosis, leukopaenia, neutropaenia, thrombocytopaenia, eosinophilia, purpura
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
Tinnitus
Alteration in EEG patterns
Paralytic ileus
Hyperpyrexia
Disturbance of accommodation
Increased intraocular pressure
Mydriasis

Pharmacology

Binding affinities

Molecular target	Amitriptyline	Nortriptyline	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-HT_1A	450	294	421	Binding for human brain receptors had to be substituted in amitriptyline and nortriptyline's cases
5-HT_2A	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 antipsychotics, clozapine, quetiapine, olanzapine, ziprasidone, risperidone, sertindole and zotepine their lower extrapyramidal side effect liability.
5-HT_2C	6.15	8.5	132	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.
α_1A	24	55	10	Human brain receptors were substituted for AMI and NOR.
α_2A	690	2030	810.5	As above.
D₂	1460	2570	0.16	As above.
D₃	206	?	0.13	Human receptors 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.