Tricyclic antidepressant

from Wikipedia, the free encyclopedia

Tricyclic antidepressants ( TCAs ), also known as non-selective monoamine reuptake inhibitors ( NSMRI ), are a group of psychotropic drugs that are primarily antidepressant . They are characterized by a mood-enhancing effect and are among the longest used substances in the treatment of depression . They are also used in ( multimodal ) pain therapy .

The term tricyclic comes from its characteristic chemical structure fragment, which consists of three fused rings. Tetracyclic antidepressants have parallels in their molecular structure and contain a four-ring system. Due to certain similarities in effect, the two groups are sometimes listed together.

Mechanism of action and classification

Tricyclic antidepressants inhibit the reuptake of the neurotransmitters serotonin , norepinephrine and dopamine in the nerve cells of the brain. The messenger substances that are increasingly available are intended to compensate for the relative lack of them typical of depression.

All active ingredients of the tricyclic antidepressants have a mood-enhancing, antidepressant effect, which usually only sets in after 2-4 weeks. Depending on the individual symptoms of the patient, substances from the following classification are used. It should be noted here that the characteristic effect of psychomotor damping or activation usually sets in at the beginning of the treatment.

  • Amitriptyline type (e.g. amitriptyline , doxepin , trimipramine ): It has a psychomotor depressant effect. In particular, the substances with a dampening action profile have a sleep-inducing and anxiolytic effect, which comes close to the effectiveness of the benzodiazepines without, however, causing addiction even with prolonged continuous use. They are mainly used for forms of depression with restlessness and anxiety, as well as for sleep disorders, isolated anxiety disorders and drug cessation.
  • Imipramine type (e.g. imipramine , clomipramine ): They predominantly inhibit 5-HT reuptake and thus show a clear anxiolytic effect, but increase drive less markedly than tricyclic antidepressants of the desipramine type; Imipramine derivatives have a drive-neutral effect or only slightly increase drive.
  • Desipramine type (e.g. desipramine , nortriptyline ): They have a psychomotor activating effect through the preferential inhibition of norepinephrine uptake and can lead to feelings of anxiety and restlessness, especially at the beginning of treatment, but in the long term they usually have an anxiolytic effect and have a positive effect on this by improving activity Sleep behavior. Since the mood-lightening, depression-relieving effect usually only occurs after a few weeks, particular caution is required with suicide-prone patients, as the immediate increase in drive can increase the risk of suicidal acts. Under certain circumstances, the bridging parallel application of an additional medication is appropriate here. These active ingredients are mainly used for depression with inhibited drive and apathy.

Individual active ingredients

application

Nowadays, tricyclic antidepressants are no longer the first choice for treating depression , as they have significantly stronger side effects than more modern antidepressants. Their effect on the neurotransmitter systems is not very selective. However, they are used for severe depression when antidepressants with a markedly selective mechanism of action (such as SSRIs ) do not show any effect. Sedating NSMRIs such as amitriptyline are used in an agitated- anxious depressive syndrome, while non-sedating NSMRIs such as nortriptyline are used in an inhibited- apathetic depressive syndrome.

Tricyclic antidepressants are also used in multimodal pain therapy .

Side effects

It will u. a. the following side effects mentioned:

Tricyclic antidepressants are metabolized via the cytochrome P450 2D6 ( CYP2D6 ). 7 percent of the population have a genetic defect in the gene that codes for the CYP 2D6 enzyme. This genetic defect can lead to a slower breakdown of these drugs, which means that toxic plasma levels can be reached and pronounced side effects occur as a result. A gene test is recommended by pharmacogenetics and the question arises whether it is still ethical in the future to treat patients with tricyclic antidepressants without a corresponding genetic test in advance.

The TCA clomipramine caused behavioral disorders in the offspring of the dams when administered prenatally and when administered during the breastfeeding phase. It is still unclear whether this can be transferred to humans and whether it also applies to other TCAs.

Some tricyclic antidepressants lead to genetic damage in the fruit fly , an increase in the risk of breast cancer is being discussed. These include clomipramine, desipramine, doxepin, imipramine and trimipramine, but not amitriptyline. Various reviews could not confirm this hypothesis.

Interactions

Tricyclic antidepressants should not be taken with other antidepressants , especially MAO inhibitors , and are available with other substances such as B. Alcohol in interaction. Taking tricyclic antidepressants (especially when combined with other drugs) can lead to the sometimes life-threatening serotonin syndrome. This is caused by uncontrollably high serotonin levels and is characterized, among other things, by high blood pressure, fever, flushing, dizziness, confusion and cramps.

Tricyclic antidepressants increase the vasoconstrictor effect of catecholamines and anticholinergic effects of other drugs and weaken the antihypertensive effect of clonidine .

Contraindications

Contraindications are glaucoma (glaucoma), pyloric stenosis , benign prostatic hyperplasia , seizure disorders and thrombosis .

Chemical structural analysis

The tricycle usually consists of two phenyl rings fused (attached) to a central seven-membered ring. A number of neuroleptics , such as the phenothiazines , have a similar tricyclic structural fragment, the central ring of which is narrowed by a methylene group (-CH 2 -) (and substitutes -CH 2 - vs. -S-). There is a difference in the degree of folding: the phenyl rings of the phenothiazines are weakly folded against each other (~ 30 °), while they are more folded in the tricyclic antidepressants (~ 50 °).

Individual evidence

  1. ↑ a b c d e F. Markus Leweke, Dagmar Koethe: General and special pharmacology and toxicology . Ed .: Klaus Aktories, Ulrich Förstermann, Franz Hofmann, Klaus Starke. 12th edition. Elsevier, Munich 2017, ISBN 978-3-437-42525-7 , pp. 273 ff .
  2. ↑ H. Lüllmann, K. Mohr, M. Wehling: Heart and circulation. In: Pharmacology and Toxicology. Understand the effects of drugs - use drugs in a targeted manner. Georg Thieme Verlag, Stuttgart / New York 2016, pp. 127–170.
  3. ↑ J. Kirchheiner, A. Seeringer, J. Brockmöller: State of pharmacogenetics in clinical drug therapy, Federal Health Gazette - Health Research - Health Protection . 49 (2006), pp. 995-1003.
  4. ^ German specialist information: Anafranil. Status: May 2007.
  5. ↑ CR Sharpe, JP Collet, E. Belzile, JA Hanley, JF Boivin: The effects of tricyclic antidepressants on breast cancer risk. In: British Journal of Cancer . Volume 86, Number 1, January 2002, pp. 92-97, doi : 10.1038 / sj.bjc.6600013 , PMID 11857018 , PMC 2746543 (free full text).
  6. ↑ DA Lawlor, P. Jüni, S. Ebrahim, M. Egger. Systematic review of the epidemiologic and trial evidence of an association between antidepressant medication and breast cancer. In: J Clin Epidemiol. 2003 Feb; 56 (2), pp. 155-63. Review. PMID 12654410 .
  7. ↑ S. Bahl, M. Cotterchio, N. Kreiger: Use of antidepressant medications and the possible association with breast cancer risk. A review. In: Psychother Psychosom. 2003 Jul-Aug; 72 (4), pp. 185-194. Review. PMID 12792123 .
  8. ^ PF Coogan: Review of the epidemiological literature on antidepressant use and breast cancer risk. In: Expert Rev Neurother . 2006 Sep; 6 (9), pp. 1363-1374. Review. PMID 17009923 .
  9. ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 173.

literature

  • Ernst Mutschler u. a .: drug effects. 8th edition. Scientific publishing company. Stuttgart 2001, ISBN 3-8047-1763-2 .

Web links

Commons : Tricyclic Antidepressant  - Collection of pictures, videos and audio files