Individual differences |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |
Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
Trimipramine chemical structure
| CAS number |
| ATC code |
| PubChem |
| DrugBank |
|Elimination half-life||11 to 23 hours, depending on metabolizer type (rapid or slow)|
|Routes of administration||Oral, im, iv|
Trimipramine's mechanism of action differs from other tricyclic antidepressants. It is only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamine. The main effects are due to considerable postynaptic blockade as follows:
- strong : 5-HT2, Muscarinic, H1, H2, Alpha1
- moderate : D2
- weak : 5-HT1, Alpha2
The spectrum of effects (strong antidepressant activity, sedation and anxiolysis) and side-effects (strong anticholinergic and antiadrenergic side-effects) is the same as with Doxepin. It is also a more effective sedative than Amitriptyline. Trimipramine is the only effective drug against insomnia known so far that does not alter the normal sleep architecture. In particular, it does not suppress REM-sleep, and dreams are said to brighten during treatment.[How to reference and link to summary or text] However, this can occasionally go too far, as nightmares are an uncommon but possible side effect of the drug. Its relatively strong antagonistic activity at postsynaptic D2-receptors led to a clinical study trying Trimipramine as atypical neuroleptic. There it exerted good antipsychotic activity with a low incidence of extrapyramidal and other side-effects. But this study encompassed only 28 patients, so the use of Trimipramine as a neuroleptic needs further confirmation and can currently not be recommended. Trimipramine shows also useful activity against chronic pain.
Trimipramine is a racemic compound with two enantiomers. CYP2C19 is responsible for the demethylation of (D)- and (L)-trimipramine to (D)- (L)-desmethyltrimipramine, respectively, and CYP2D6 is responsible for the 2-hydroxylation of (D)- and (L)-desmethyltrimipramine to (D)- and (L)-2-hydroxydesmethyltrimipramine, respectively. CYP2D6 also metabolizes (L)-trimipramine into (L)-2-hydroxytrimipramine
- Endogenous and neurotic depression with prominent agitation and anxiety
- Depressive and non-depressive insomnia (suitable for long-term treatment)
- Adjunctive therapy of alcohol and opioid withdrawal
- Chronic pain of malignant and non-malignant origin
Trimipramine is an efficient antidepressant, sedative, and anxiolytic comparable to Doxepin.
- concomitant treatment with MAO-Inhibitors
- known hypersensitivity to Trimipramine or other Tricyclics
- acute intoxication with alcohol, sedatives, analgesics and other psychoactive drugs
- acute Delirum tremens
- untreated closed angle glaucoma
- hypertrophy of the prostate with urine retention
- paralytic ileus
- hypertrophy of the prostate without urine retention
- reduced function of the bone marrow
- organic brain disorders
- increased risk of seizures, preexisting epilepsy
- preexisting cardial damage, particular some arrhythmias (impulse conductive disorders)
- Further information: Doxepin
All side-effects of Doxepin are noted also during Trimipramine use with approximately the same frequency and intensity in equivalent doses.
Additionally, very unusual hypersensitivity reactions involving blood (eosinophilia), liver (diffuse liver damage), lung (eosinophilic pleuritis) and flu-like symptoms have been rarely noted and should be carefully watched for.
With other centrally active substances and drugs that interfere with the metabolization and elimination.
Drug Abuse and Dependence
Trimipramine is not an abusable substance nor does it cause psychological dependence.
Withdrawal symptoms frequently seen when treatment with Trimipramine is stopped abruptly (agitation, anxiety, insomnia, sometimes activation of mania or rebound depression) are not indicative of addiction and can be avoided by reducing the daily dose of Trimipramine gradually by approximately 25% each week. If treatment has to be stopped at once due to medical reasons, the use of a benzodiazepine (e.g. Lorazepam, Clonazepam, or Alprazolam) for a maximum of 4 weeks as needed will usually suppress withdrawal symptoms.
Necessary Examinations during Treatment
The examinations needed depend on the risk profile of the patient. In most cases, particular with high doses, frequent blood pressure and EKG-profiles are indicated. All patients should have periodical laboratory checks including white bloodcell counts, liver-, and kidney-function tests. Patients with risks for development of seizures may also need EEG-examinations.
The following recommendations are for the treatment of depression. The proper dosage for treatment of insomnia in non-depressive patients, those on alcohol/opioid withdrawal and those with chronic pain may vary greatly and should be discussed with your physician.
Treatment should be initiated at the lowest recommended dose and increased gradually, noting carefully the clinical response and any evidence of intolerance. Days to weeks may elapse before optimal therapeutic effects of Trimipramine are seen. Increasing the dosage usually does not shorten this latent period and may increase the incidence of side effects and patient non-compliance.
- Adults with mild or moderate disease:
The recommended initial dose is 75 mg daily in two or three divided doses. Initial tolerance may be tested by giving the patient 25 mg on the evening of the first day. The initial dose can be increased by 25 mg increments, usually up to 150 mg daily, preferably by adding to the late afternoon and/or bedtime doses. The greater part of the daily dose should be given in the late afternoon or at bedtime to minimize bothersome daytime sedation.
- Adults with severe disease:
In the case of severely depressed patients, a higher initial dose of 100 mg daily in two or three divided doses may be indicated. The usual optimal dose is 150 mg to 200 mg daily, but some patients may require up to 300 mg (or even 400mg) daily, depending on tolerance and response of each individual patient. Preferably, hospititalize patients requiring more than 150mg daily, because the side-effects can be very intense.
- Elderly or debilitated patients:
In these patients it is advisable to give a test dose of 12.5 to 25 mg and after 45 minutes examine the patient sitting and standing to check for orthostatic hypotension. Initial doses should usually be no more than 50 mg a day in divided doses, with weekly increments of no more than 25 mg a week, leading to a usual therapeutic dose range of 60 to 150 mg a day. Blood pressure and cardiac rhythm should be checked frequently, particularly in patients who have unstable cardiovascular function.
- Maintenance Dosage:
Once a satisfactory response has been obtained, the dosage should be adjusted to the lowest level required to maintain remission and avoid relapse. Medication should be continued for the expected duration of the depressive episode in order to minimize the possibility of relapse following clinical improvement. Afterwards, prophylactic treatment for 1 to 2 years may be indicated, but there are different opinions regarding the optimal dose and length of remission maintenance treatment.
When a maintenance dosage has been established as described above, Trimipramine may be administered in a single dose before bedtime, provided such a dosage regimen is well tolerated.
Intramuscular injections and slow i.v.-infusions are possible, but have the disadvantage of intensified anticholinergic and antiadrenergic side-effects. The advantage may be an earlier onset of action compared to oral dosage. Decreased doses are sufficient with parenteral treatment.
Usual Dosage Forms
- tablets/capsules 10, 12.5, 25, 50, 75, 100, 150mg
- liquid concentrate (40mg/ml)
- injectable concentrate (25mg)
- Stangyl ®
- Surmontil ®
- Rhotrimine ®
References and End Notes
- B. Bandelow, S. Bleich, S. Kropp : Handbuch Psychopharmaka (German), 2nd. edition, 2004
- Barocka et al. : Psychopharmakatherapie in Klinik und Praxis (German), 1998
- Benkert, Hippius : Kompendium der Psychiatrischen Pharmakotherapie, 4th. edition, 2003
- PubChem Substance Summary: Trimipramine National Center for Biotechnology Information.
- information page mentalhealth
|This page uses Creative Commons Licensed content from Wikipedia (view authors).|