Depression Symptoms Treatment

Interactions

Interactions involving tricyclic antidepressants often result from additive toxicity or from altered metabolism of one drug by the other. Drugs that inhibit or induce the cytochrome P450 isoenzyme CYP2D6 may affect tricyclic metabolism and produce marked alterations in plasma concentrations. Adverse effects may be enhanced by antimuscarinic drugs or CNS depressants, including alcohol. Barbiturates and other enzyme inducers such as rifampicin and some antiepileptics can increase the metabolism of tricyclic antidepressants and may lower plasma concentrations and reduce antidepressant response. Cimetidine, methylphenidate, antipsychotics, and calcium-channel blockers can reduce the metabolism of the tricyclics, leading to the possibility of increased plasma concentrations and accompanying toxicity. Patients taking thyroid preparations may show an accelerated response to tricyclic antidepressants and occasionally liothyronine has been used to produce this effect in patients with refractory depression. However, the use of tricyclics with thyroid hormones may precipitate cardiac arrhythmias.

The antihypertensive effects of debrisoquine, guanethidine, and clonidine may be reduced by tricyclic antidepressants. The pressor effects of sympathomimetics, especially those of the direct-acting drugs adrenaline and noradrenaline, can be enhanced by tricyclic antidepressants however, there is no clinical evidence of dangerous interactions between adrenaline-containing local anaesthetics and tricyclic antidepressants. Great care should, however, be taken to avoid inadvertent intravenous injection of the local anaesthetic preparation.

Drugs that prolong the QT interval, including antiarrhythmics such as amiodarone or quinidine, the antihistamines astemizole and terfenadine, some antipsychotics (notably pimozide, sertindole, and thioridazine), cisapride, halofantrine, and sotalol, may increase the likelihood of ventricular arrhythmias when taken with tricyclic antidepressants. This may be exacerbated where the interacting drug (such as quinidine or some antipsychotics) also reduces tricyclic metabolism.

Although different antidepressants have been used together under expert supervision in refractory cases of depression, severe adverse reactions including the serotonin syndrome (see) may occur. For this reason an appropriate drug-free interval should elapse between stopping some types of antidepressant and starting another. Tricyclic antidepressants should not generally be given to patients receiving MAOIs or for at least 2 weeks (3 weeks if starting clomipramine or imipramine) after their withdrawal. No treatment-free period is necessary after stopping a reversible inhibitor of monoamine oxidase type A (RIMA) and starting a tricyclic. At least 1 to 2 weeks (3 weeks in the case of clomipramine or imipramine) should elapse between withdrawing a tricyclic antidepressant and starting any drug liable to provoke a serious reaction (e.g. phenelzine).

Further details concerning some of the above interactions, and others, are given below.

Alcohol. For reference to the effect of alcohol on amitriptyline, see under CNS depressants, below.

Analgesics. Doubling of plasma-doxepin concentrations with associated lethargy has been reported in a patient after the addition of dextropropoxyphene to the tricyclic. This was consistent with previous studies indicating that dextropropoxyphene can impair the hepatic metabolism of other drugs.

For general reference to the effect of tricyclic antidepressants, notably amitriptyline and clomipramine, on opioid analgesics, see under Morphine.

Antiarrhythmics. Antiarrhythmics that prolong the QT interval may increase the likelihood of ventricular arrhythmias when given with tricyclic antidepressants. This includes various class I antiarrhythmics such as disopyramide,flecainide,procainamide, propafenone, and quinidine, and the class III antiarrhythmic amiodarone.

Raised serum- desipramine concentrations and signs of toxicity were noted in a patient taking desipramine after starting treatment with digoxin and propafenone for paroxysmal atrial fibrillation. It was considered that propafenone probably reduced the metabolism and clearance of desipramine.

Anticoagulants. For the effect of tricyclic antidepressants on anticoagulants, see under Warfarin.

Antidepressants. Combination therapy with differing classes of antidepressants has been used successfully in the treatment of drug-resistant depression. It should be emphasised, however, that such combinations may result in interactions or enhanced adverse reactions, and should be used only under expert supervision. This practice is considered unsuitable or controversial by some authorities. For further details of the interactions between different antidepressants when used together, see Phenelzine. For details of the serotonin syndrome that can arise when two serotonergic drugs with different mechanisms of action are given, see under Adverse Effects of Phenelzine.

Antid iabetics. For the effect of tricyclic antidepressants on sulfonylureas and insulin, see Interactions, respectively.

Antiepileptics. Antidepressants may antagonise the activity of antiepileptics by lowering the convulsive threshold. A review of drug interactions with phenytoin noted that although there had been reports of interactions between antiepileptics and tricyclic or related antidepressants, most involved enzyme-inducing antiepileptics other than phenytoin or phenytoin with other drugs. In the only report where phenytoin could be identified as the sole antiepileptic used, 2 patients required high doses of desipramine to achieve an antidepressant effect and to maintain plasma-desipramine concentrations in the range usually associated with therapeutic efficacy.

Carbamazepine has been reported to induce the metabolism of a number of tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, and nortriptyline) and to reduce their plasma concentrations. The clinical importance of the interaction is unclear. Use of nortriptyline with carbamazepine in a patient led to a decrease in serum-nortriptyline concentration requiring an increase in nortriptyline dose. In another patient a prolonged QT interval was noted after use of desipramine with carbamazepine the authors hypothesised that the accelerated metabolism of desipramine had resulted in high levels of a cardiotoxic metabolite.

Valproate has been reported to increase plasma concentrations of amitriptyline, clomipramine, and nortriptyline. For the effect of the cyclic antidepressants desipramine and viloxazine on carbamazepine. For the effects of tricyclic antidepressants on phenytoin.

Antifungals. Increased serum concentrations of nortriptyline or amitriptyline’ have occurred in patients also taking fluconazole. In some patients the use of amitriptyline with fluconazole has led to syncope or torsade de pointes. Raised serum concentrations of nortriptyline and associated symptoms of intoxication have been reported in 2 patients during treatment with terbinafine the interaction was confirmed on rechallenge. In another case, dizziness, dry mouth, and muscle twitching were reported in a patient on long-term imipramine treatment after starting terbinafme serum imipramine concentrations were found to be elevated and symptoms subsided after the dose of imipramine was reduced. A study in healthy subjects also indicated that terbinafine similarly inhibited the metabolism of desipramine.

Antihypertensives. In general, the hypotensive effect of anti-hypertensives is enhanced by tricyclic antidepressants, but there may be antagonism of the effect of adrenergic neurone blockers and of clonidine.

Antimigraine drugs. For the effects when some tricyclics are used with dihydroergoiamine.

A nti neoplasties. For the effects when tricyclic antidepressants are used with altretamine.

Antiprotozoals. Toxic psychosis developed in a patient on amitriptyline after starting furazolidone, an antiprotozoal with monoamine oxidase inhibiting activity.

Antipsychotics. For a discussion of interactions between antipsychotics and tricyclic antidepressants, see Chlorpromazine. For details of a possible interaction between clomipramine and clozapine.

Antivirals. HIV-protease inhibitors may increase the plasma concentrations of tricyclic antidepressants whose metabolism is mediated through common cytochrome P450 isoenzymes. Ritonavir has produced moderate increases in the plasma concentrations of desipramine and a lower initial dose of desipramine may be appropriate. Ticensed product information for ritonavir has warned that a similar increase may occur for other tricyclics monitoring of therapeutic and adverse effects is recommended when tricyclics are used with ritonavir.

Anxiolytics. For a suggestion that benzodiazepines may increase the oxidation of amineptine to a toxic metabolite, see under Effects on the Tiver in Adverse Effects, above. For a possible interaction of desipramine and other antidepressants with zolpidem.

Barbiturates. Antidepressants may antagonise the antiepileptic activity of some barbiturates by lowering the convulsive threshold.

Barbiturates can increase the metabolism of tricyclic antidepressants and thereby produce lower plasma concentrations. For details of the interaction of tricyclic antidepressants with barbiturate anaesthetics, see under Anaesthesia in Precautions, above.

Beta blockers. Raised imipramine plasma concentrations were noted in two 9-year-old children also given propranolol in both cases, no significant adverse effects were reported. Labetalol has also increased the bioavailability of imipramine in healthy subjects and inhibited its metabolism.

The risk of ventricular arrhythmias may be increased when tricyclic antidepressants are taken with sotalol.

Calcium-channel blockers. Diltiazem and verapamil each increased the bioavailability of imipramine in healthy subjects second-degree heart block developed in 2 subjects. Diltiazem also increased the bioavailability of nortriptyline in one patient, probably by reducing the first-pass metabolism of nortriptyline. Increased serum concentrations of trimipramine have been reported when taken with diltiazem, although there was no evidence of toxicity.

CNS depressants. Drugs with depressant actions on the CNS may be expected to enhance the drowsiness and related effects produced by the sedating type of tricyclic antidepressants. Such an interaction may occur between alcohol and tricyclic antidepressants and a study has shown that alcohol decreases the hepatic first-pass extraction of amitriptyline resulting in increased free plasma-amitriptyline concentrations, especially during the period of drug absorption.

The problems that may be encountered with barbiturate anaesthetics are discussed under Anaesthesia in Precautions, above.

Disulfiram. Acute organic brain syndrome has been reported in 2 patients receiving disulfiram after the addition of amitriptyline to their treatment. It was suspected that the syndrome was potentiated by the combined action of the drugs and the synergistic elevation in dopamine concentration.

For a report of the enhancement of the disulfiram-alcohol reaction by amitriptyline.

Dopaminergics. Serious adverse effects have been reported when selegiline, an irreversible selective inhibitor of monoamine oxidase type B, was used with tricyclic antidepressants. In some instances effects resembled the potentially fatal serotonin syndromes reported when tricyclics are given with non-selective MAO Is (see under Phenelzine).

Some manufacturers of selegiline advise that tricyclic antidepressants should not generally be given at the same time, or for at least 2 weeks after it has been discontinued. Similarly, at least one week should elapse between withdrawing a tricyclic antidepressant and starting selegiline.

For reference to the effect of tricyclic antidepressants on levodopa.

General anaesthetics. For the effect of amitriptyline on enflurane. For the effects of using tricyclic antidepressants with barbiturates see under Anaesthesia in Precautions, above.

Histamine H₂-antagonists. Cimetidine is a known inhibitor of hepatic metabolism of drugs and symptoms of tricyclic toxicity have been reported in patients receiving cimetidine with desipramine, doxepin, and imipramine there has been a report of psychosis developing in a patient given imipramine and cimetidine. Elevated tricyclic concentrations during combined therapy or reductions in tricyclic concentrations after withdrawal of cimetidine have been reported for imipramine and nortriptyline. Studies in healthy subjects have also indicated increased bioavailability and/or impaired hepatic metabolism of amitriptyline, doxepin, and imipramine during cimetidine therapy. Adjustment of tricyclic antidepressant dosage may therefore be required if cimetidine therapy is begun or stopped. Ranitidine has been reported not to alter the pharmacokinetics of amitriptyline, doxepin, or imipramine.

Muscle relaxants. There has been an isolated report of a patient taking baclofen for spasticity who experienced leg weakness and was unable to stand after starting treatment with nortriptyline. Symptoms improved on stopping nortriptyline but recurred when imipramine was given.

Sex hormones. There have been anecdotal reports of interactions between tricyclic antidepressants and oestrogens resulting in a lack of antidepressant response and/or tricyclic toxicity the significance of these interactions is not, however, established.

Smoking. Tobacco smoke has been reported to reduce the plasma levels of tricyclic antidepressants. The clinical significance is not, however, fully established as the plasma concentration of unbound drug may not be affected. The mechanism is probably by stimulation of hepatic drug metabolism by components present in cigarette smoke.

Sympathomimetics. The pressor effects of sympathomimetics can be enhanced by tricychc antidepressants. For precautions to be observed in patients on tricychc therapy who may require sympathomimetics during anaesthesia, see under Anaesthesia in Precautions, above.

Thyroid hormones. An increase in receptor sensitivity to catecholamines produced by thyroid hormones has been proposed as the reason for an increase in response to tricyclic antidepressants given with liothyronine.

Pharmacokinetics

Amitriptyline is readily absorbed from the gastrointestinal tract, peak plasma concentrations occurring within about 6 hours after oral doses. Amitriptyline undergoes extensive first-pass metabolism and is demethylated in the liver by the cytochrome P450 isoenzymes CYP3A4, CYP2C9, and CYP2D6 to its primary active metabolite, nortriptyline. Other paths of metabolism of amitriptyline include hydroxylation (possibly to active metabolites) by CYP2D6 and N-oxidation nortriptyline follows similar paths. Amitriptyline is excreted in the urine, mainly in the form of its metabolites, either free or in conjugated form. Amitriptyline and nortriptyline are widely distributed throughout the body and are extensively bound to plasma and tissue protein. Amitriptyline has been estimated to have an elimination half-life ranging from about 9 to 25 hours, which may be considerably extended in overdosage. Plasma concentrations of amitriptyline and nortriptyline vary very widely between individuals and no simple correlation with therapeutic response has been established.

Amitriptyline and nortriptyline cross the placenta and are distributed into breast milk (see Breast Feeding under Precautions, above).

Uses and Administration

Tricyclic antidepressants such as amitriptyline were developed from phenothiazine compounds related to chlorpromazine and, as the name suggests, possess a 3-ring molecular structure. They inhibit the neuronal reuptake of noradrenaline in the CNS some, in addition, inhibit the reuptake of serotonin (5-HT). Prevention of the reuptake of these monoamine neurotransmitters, which potentiates their action in the brain, appears to be associated with antidepressant activity. Tricyclic antidepressants also possess affinity for muscarinic and histamine H1 receptors to varying degrees, see under Adverse Effects, above. Amitriptyline is one of the more sedating tricyclics. Antidepressants with one, two, or four rings have also been developed, and these share only some of the properties of the tricyclics. While the sedative action and other adverse effects of amitriptyline and other tricyclics are soon apparent, it may be several weeks before any antidepressant effect is seen. After a response has been obtained, maintenance therapy should be continued at the optimum dose for at least 4 to 6 months (12 months in the elderly) to avoid relapse on stopping therapy. Patients with a history of recurrent depression should continue to receive maintenance treatment for at least 5 years and possibly indefinitely. It is important to use doses that are sufficiently high for effective treatment, but not so high as to cause toxic effects.

Amitriptyline, a dibenzocycloheptadiene, is usually given orally as the hydrochloride and doses are expressed in terms of this salt. Amitriptyline hydrochloride is also given by intramuscular or slow intravenous injection doses may be expressed in terms of the base or the hydrochloride. Amitriptyline hydrochloride 75 mg is equivalent to about 66.3 mg of the base. Amitriptyline has also been given orally as the embonate and as the oxide (amitriptylinoxide). In the treatment of depression, amitriptyline hydrochloride is given initially in a daily dose of 50 to 75 mg orally in divided doses (or as a single dose at night). Thereafter, the dose may be gradually increased, if necessary, to 150 mg daily, the additional doses being given in the late afternoon or evening. Doses of up to 200 mg daily and, occasionally, up to 300 mg daily have been used in severely depressed patients in hospital.

Adolescent and elderly patients often have reduced tolerance to tricyclic antidepressants and UK licensed drug information states that initial doses of amitriptyline hydrochloride as low as 25 mg daily may be used in these groups, given either in divided doses or as a single dose, preferably atbedtime. TheBNFsuggests a minimum initial dose of 30 mg daily. In the UK, the use of amitriptyline in children under 16 years for the treatment of depression is not recommended. In the initial stages of treatment, if dosage by mouth is impracticable or inadvisable, amitriptyline hydrochloride may be given by intramuscular injection, but the oral route should be substituted as soon as possible. Doses are similar to those usually given orally. The intravenous route has also been used. Amitriptyline is also used for the treatment of nocturnal enuresis in children in whom organic pathology has been excluded. However, drug therapy for nocturnal enuresis should be reserved for when other methods have failed and should preferably only be given to cover periods away from home tricyclic antidepressants are not recommended in children under 6 years of age (the BNF recommends that they should not be given until 7 years of age). Oral doses of amitriptyline hydrochloride that may be used are:

• 10 to 20 mg for children aged 6 to 10 years

• 25 to 50 mg for children 11 years and over

The dose should be given 30 minutes before bedtime and treatment, including a period of gradual withdrawal, should not continue for longer than 3 months. A full physical examination is recommended before a further course.

Tricyclic antidepressants, including amitriptyline, may be helpful in some anxiety disorders such as panic disorder, and in the management of neuropathic pain (see below).

Amitriptyline should be withdrawn gradually to reduce the risk of withdrawal symptoms.

Anxiety disorders. For the use of tricyclic antidepressants in anxiety disorders, see under Clomipramine.

Bulimia nervosa. A combination of counselling, support, psychotherapy, and antidepressants is the usual treatment for bulimia nervosa. Antidepressants can help to reduce the frequency of overeating and some other symptoms of bulimia but relapse tends to occur when stopped. Many antidepressants have been tried, but the tricyclic desipramine and the SSRI fiuoxetine have been the most commonly used and are considered to be well tolerated. References.

Ciguatera poisoning. Amitriptyline has relieved some of the neurological symptoms associated with ciguatera poisoning (see Mannitol).

Cocaine dependence. For the use of tricyclic antidepressants in cocaine dependence, see under Desipramine.

Depression. As discussed, there is very little difference in efficacy between the different groups of antidepressant drugs, and choice is often made on the basis of adverse effect profile. Although less well tolerated than the newer antidepressants, tricyclic antidepressants may still be chosen because of wide experience with their use and familiarity with their pharmacological actions. The more sedating tricyclics such as amitriptyline, clomipramine, dosulepin, doxepin, and trimipramine may be of value in depression with associated agitation or anxiety. The less sedating tricyclics such as amoxapine, desipramine, imipramine, lofepramine, nortriptyline, and protriptyline may be of value for withdrawn or apathetic depressed patients. Combination therapy with differing classes of antidepressants, including the tricyclics, has been used in the treatment of refractory or drug-resistant depression. However, such therapy may result in enhanced adverse reactions or interactions and requires expert supervision it is considered unsuitable or controversial by some. For further details, see Antidepressants under Interactions of Phenelzine.

Headache. Tricyclic antidepressants can be effective in the management of some types of headache and, although they are especially useful when the headache is accompanied by depression, their beneficial effects appear to be independent of their antidepressant action. They are used for the prophylaxis of migraine when drugs such as propranolol have proved ineffective. Amitriptyline is the tricyclic usually used but others have been tried. It has also been investigated in children. The BNF suggests an adult dosage for amitriptyline in the prophylaxis of migraine of 10 mg at night, increased to a maintenance dose of 50 to 75 mg at night the need for continuing prophylaxis should be reviewed at intervals of about 6 months. Tricyclics are also used prophylactic ally in the control of chronic tensiontype headache although benefit is rarely complete. Improvement is generally seen with low doses, but full antidepressant doses are necessary in the presence of underlying depression. References.

Hiccup. Amitriptyline is one of many drugs for which there are anecdotal reports of success in the treatment of intractable hiccup.

Hyperactivity. When drug therapy is required for attention deficit hyperactivity disorder, initial treatment is usually with a central stimulant. Tricyclic antidepressants such as imipramine or desipramine are reserved for patients who fail to respond to or who are intolerant of stimulants. They may also be of use for selected patients with certain co-existing disorders.

Interstitial cystitis. Tricyclic antidepressants have been found to be of benefit in the treatment of interstitial cystitis. In a placebo-controlled trial in 48 patients with interstitial cystitis, amitriptyline treatment (in doses ranging from 25 to 100 mg daily) significantly reduced the symptom score and improved pain and urgency when compared to placebo however, in some patients the antimuscarinic adverse effects of amitriptyline were troublesome. Amitriptyline or imipramine have also been given at night, together with methenamine hippurate during the day, in the treatment of interstitial cystitis.

Irritable bowel syndrome. A tricyclic antidepressant may be tried in irritable bowel syndrome, particularly where diarrhoea and abdominal pain are presenting symptoms.

Micturition disorders. Tricyclic antidepressants are among the drugs used as an alternative or adjunct to nonpharmacological methods for the treatment of nocturnal enuresis in children

in whom organic pathology has been excluded. However, because of their potentially fatal toxicity in overdosage, there has been concern over the safety of using tricyclics in households with children. Most experience in nocturnal enuresis has been with imipramine, but other tricyclics such as amitriptyline, nortriptyline, and clomipramine have also been used. Their mechanism of action in nocturnal enuresis is unclear. It may be the result of their antimuscarinic and antispasmodic actions as well as their effect on sleep patterns and possible stimulation of antidiuretic hormone secretion. Imipramine appears to be most effective in older children, but many patients develop tolerance and increasingly higher doses are required. Tricyclic antidepressants are also sometimes used in the management of urinary incontinence.

Narcoleptic syndrome. Tricyclic antidepressants are the primary treatment for cataplexy and sleep paralysis associated with narcolepsy. Imipramine has been widely used for these symptoms although some consider clomipramine more effective. The onset of action is quicker than when used for depression and doses required appear to be lower (typically 10 to 75 mg of imipramine daily) although tolerance may develop. Doses should be titrated to provide maximal protection for the time of day when symptoms usually occur.

Pain. Tricyclic antidepressants, usually amitriptyline, are useful in alleviating some types of pain when given in subantidepres-sant doses. An initial oral dose of amitriptyline hydrochloride 10 to 25 mg at night increased gradually if necessary to about 75 mg daily has been suggested by the BNF for the management of neuropathic pain in adults. Similar doses of amitriptyline hydrochloride are also suggested by the BNFC for the treatment of neuropathic pain in palliative care in children aged 12 years and over in addition, younger children aged 2 years and above may receive an initial dose of 200 to 500 micrograms/kg (to a maximum of 25 mg) once daily at night, increased if necessary to a maximum of 1 mg/kg twice daily. See also Choice of Analgesic on p.2. Chronic neuropathic pain as seen in cancer, central post-stroke pain, diabetic neuropathy, phantom limb pain, and postherpetic neuralgia responds to therapy with tricyclics. Tricyclics are also often of benefit in the treatment of idiopathic orofacial pain, and may be of value for patients with complex regional pain syndrome. Pain and sleep quality may be improved by tricyclics in patients with fibromyalgia (see Soft-tissue Rheumatism), a condition that responds poorly to analgesics and anti-inflammatory drugs. Patients with migraine or chronic tension-type headache may also benefit from tricyclics (see Headache, above). There is little evidence for an analgesic effect of tricyclics in acute or arthritic pain. References.

Pathological crying or laughing. Pathological crying or laughing can result from lesions in certain areas of the brain. Attempts at treatment have mostly been with antidepressants and favourable results have been reported in double-blind studies with amitriptyline and nortriptyline.

Premenstrual syndrome. For reference to the tricyclic antidepressant, clomipramine, in premenstrual syndrome.

Schizophrenia. Antidepressants such as the tricyclics are considered worth trying as an adjunct in the treatment of patients with schizophrenia who develop depression during the recovery phase after an acute episode of psychosis. There is, however, no clear evidence that they are effective during acute psychotic episodes or for depression during periods of remission in patients with chronic schizophrenia.

Sexual dysfunction. Impotence or ejaculatory problems have been reported as adverse effects of tricyclic antidepressants.

Effects on Sexual Function in Adverse Effects, above). Such properties have been studied as a potential form of treatment for men with premature ejaculation (see Clomipramine).

Skin disorders. See under Doxepin, for use of tricyclic antidepressants in skin disorders.

Smoking cessation. Tricyclic antidepressants are among the drugs that have been tried with varying degrees of success as alternatives to nicotine replacement therapy (NRT) to alleviate the withdrawal syndrome associated with smoking cessation. Nortriptyline is recommended by some as a second-line treatment in those patients who cannot tolerate or relapse after NRT. References.

Preparations

British Pharmacopoeia 2008: Amitriptyline Tablets

The United States Pharmacopeia 31, 2008: Amitriptyline Hydrochloride Injection Amitriptyline Hydrochloride Tablets Chlordiazepoxide and Amitriptyline Hydrochloride Tablets Perphenazine and Amitriptyline Hydrochloride Tablets.

Proprietary Preparations

Argentina: Tryptanol Uxen

Australia: Endep Tryptanol

Austria: Saroten Tryptizol

Belgium: Redomex Tryptizol

Brazil: Amytril Neurotrypt Protanol Tripsol Tryptanol

Canada: Elavilf Novo-Triptyn

Denmark: Saroten Tryptizol

Finland: Saroten † Triptyl

France: Elavil Laroxyl

Germany: Amineurin Amioxid Equilibria Novoprotect Saroten Syneudon

Greece: Maxivalet Saroten Stelminal

Hong Kong: Qualitriptine Tryptanol

Hungary: Teperin

India: Sarotena Tryptomer

Ireland.: Lentizoll

Israel: Elatrol Elatrolet Tryptal

Italy: Adepril Laroxyl Triptizol

Malaysia: Endep Tripta Tryptanol

Mexico: Anapsique Tryptanol

Norway: Sarotex Tryptizol

New Zealand: Amitrip

Portugal: ADT Tryptizol

Russia: Amyzol Eliwel Saroten

South Africa: Noriline Saroten Trepiline Tryptanol

Singapore Tripta

Spain: Deprelio Tryptizol

Sweden: Saroten Tryptizol

Switzerland: Saroten Tryptizol

Thailand: Polytanol Tripsyline † Tripta Triptyline Tryptanol

Turkey: Laroxyl Triptilin

UK: Elavil

USA: Elavil

Venezuela: Tryptanol

Multi-ingredient

Argentina: Mutabon D

Austria: Limbitrol

Brazil: Lirnbitrol

Canada: PMS-Levazine Triavil

Chile: Antalin Limbatrilin Morelin Mutabon D Tiperin

Finland: Klotriptyl Limbitrol Pertriptyl

Greece: Minitran

India: Emotrip

Indonesia: Limbritol Mutabon-D Mutabon-M

Italy: Diapatol Limbitryl Mutabon Sedans

Mexico: Adepsique

Portugal: Mutabon

Russia: Amixide

South Africa: Etrafonl Limbitrol

Spain: Mutabase Nobritol

Switzerland: Limbitrol

Thailand: Anxipress-Df Neuragon Polybon

UK: Triptafen

USA: Etrafon Limbitrol Triavil