Jump to content

Tricyclic antidepressant

From Wikipedia, the free encyclopedia

Tricyclic antidepressant
Drug class
Chemical structure of the prototypical and first marketed tricyclic antidepressant imipramine showing its three rings.
Class identifiers
Chemical classTricyclic
External links
MeSHD000929
Legal status
In Wikidata

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade.[1] They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs.[2]

Medical uses

[edit]

The TCAs are used primarily in the clinical treatment of mood disorders such as major depressive disorder (MDD), dysthymia, and treatment-resistant variants. They are also used in the treatment of a number of other medical disorders, including cyclic vomiting syndrome (CVS) and anxiety disorders such as generalized anxiety disorder (GAD), social phobia (SP) also known as social anxiety disorder (SAD), obsessive-compulsive disorder premature ejaculation (clomipramine) and panic disorder (PD), post-traumatic stress disorder (PTSD), body dysmorphic disorder (BDD), eating disorders like anorexia nervosa and bulimia nervosa, certain personality disorders such as borderline personality disorder (BPD) and Avoidant personality disorder(AvPD) neurological disorders such as attention-deficit hyperactivity disorder (ADHD),[3] Parkinson's disease[4] as well as chronic pain, neuralgia or neuropathic pain, Complex regional pain syndrome and fibromyalgia, headache, or migraine, smoking cessation, tourette syndrome, trichotillomania, irritable bowel syndrome (IBS), interstitial cystitis (IC), nocturnal enuresis (NE),[5] narcolepsy, insomnia, pathological crying and/or laughing, chronic hiccups, ciguatera poisoning, and as an adjunct in schizophrenia and certain psychotic disorders

Nortriptyline and desipramine may be preferred medications over other TCAs among older adults due to their reduced anticholinergic effects, diminished cardiac toxicity, and more linear pharmacokinetics.[6][7]

Clinical depression

[edit]

For many years the TCAs were the first choice for pharmacological treatment of major depression. Although they are still considered to be effective, they have been increasingly replaced by antidepressants with an improved safety and side-effect profile, such as the SSRIs and other newer antidepressants such as the novel reversible MAOI moclobemide. However, TCAs have been claimed to possibly be more effective in treating melancholic depression than other antidepressant drug classes.[8] Newer antidepressants are thought to have fewer and less severe side effects and are also thought to be less likely to result in injury or death if used in a suicide attempt, as the doses required for clinical treatment and potentially lethal overdose (see therapeutic index) are far wider in comparison.

Nonetheless, the TCAs are commonly prescribed for treatment-resistant depression that has failed to respond to therapy with newer antidepressants, they also tend to have fewer emotional blunting and sexual side effects than SSRI antidepressants.[9] They are not considered addictive and are somewhat preferable to the monoamine oxidase inhibitors (MAOIs). The side effects of the TCAs usually come to prominence before the therapeutic benefits against depression and/or anxiety do, and for this reason, they may potentially be somewhat dangerous, as volition can be increased, possibly giving the patient a greater desire to attempt or commit suicide.[10]

A 2024 systematic review and meta-analysis assessed the beneficial and harmful effects of TCAs in the treatment of major depressive disorder in adults.[11] Previous systematic reviews and meta-analyses had not comprehensively assessed TCAs in the same fashion, with the largest including only two TCAs (amitriptyline and clomipramine) and only 36 trials.[11][12] A total of 103 short-term clinical trials with 10,590 participants employing 12 different TCAs (and TeCAs) were included.[11] TCAs showed a small benefit on depression over that of placebo in terms of reduction in Hamilton Depression Rating Scale-17 (HDRS-17) scores (mean difference: –3.77 points; or with removal of an outlier study: –3.16 points).[11] Due to the possibility of unblinding by side effects, it was unclear whether TCAs had a genuine antidepressant effect or whether the benefits were merely due to amplified placebo effects.[11] TCAs had a higher rate of serious adverse effects than placebo, but this did not reach statistical significance (ORTooltip odds ratio = 2.78; 95% CI: 2.18–3.55; k = 35).[11] The quality of evidence was low to very low and the results were at high risk of bias.[11] Among the collaborators of the systematic review and meta-analysis included Irving Kirsch, Joanna Moncrieff, and Michael P. Hengartner.[11]

Attention-deficit hyperactivity disorder

[edit]

The TCAs were used in the past in the clinical treatment of ADHD,[13] though they are not typically used anymore, having been replaced by more effective agents with fewer side effects such as atomoxetine (Strattera, Tomoxetin) and stimulants like methylphenidate (Ritalin, Focalin, Concerta), and amphetamine (Adderall, Attentin, Dexedrine, Vyvanse). ADHD is thought to be caused by an insufficiency of dopamine and norepinephrine activity in the prefrontal cortex of the brain.[14] Most of the TCAs inhibit the reuptake of norepinephrine, though not dopamine, and as a result, they show some efficacy in remedying the disorder.[15] Notably, the TCAs are more effective in treating the behavioral aspects of ADHD than the cognitive deficits, as they help limit hyperactivity and impulsivity, but have little to no benefits on attention.[16]

Chronic pain

[edit]

The TCAs show efficacy in the clinical treatment of a number of different types of chronic pain, notably neuralgia or neuropathic pain and fibromyalgia.[17][18] The precise mechanism of action in explanation of their analgesic efficacy is unclear, but it is thought that they indirectly modulate the opioid system in the brain downstream via serotonergic and noradrenergic neuromodulation, among other properties.[19][20][21] They are also effective in migraine prophylaxis,[22] though not in the instant relief of an acute migraine attack. They may also be effective to prevent chronic tension headaches.

Side effects

[edit]

Many side effects may be related to the antimuscarinic properties of the TCAs. Such side effects are relatively common and may include dry mouth, dry nose, blurry vision, lowered gastrointestinal motility or constipation, urinary retention, cognitive and/or memory impairment, and increased body temperature.

Other side effects may include drowsiness, anxiety, emotional blunting (apathy/anhedonia), confusion, restlessness, dizziness, akathisia, hypersensitivity, changes in appetite and weight, sweating, muscle twitches, weakness, nausea and vomiting, hypotension, tachycardia, and rarely, irregular heart rhythms. Twitching, hallucinations, delirium and coma are also some of the toxic effects caused by overdose.[23] Rhabdomyolysis or muscle breakdown has been rarely reported with this class of drugs as well.[24]

Delayed ejaculation may be experienced by some tricyclic antidepressants such as clomipramine

Tolerance to these adverse effects of these drugs often develops if treatment is continued. Side effects may also be less troublesome if treatment is initiated with low doses and then gradually increased, although this may also delay the beneficial effects.

TCAs can behave like class 1A antiarrhythmics, as such, they can theoretically terminate ventricular fibrillation, decrease cardiac contractility and increase collateral blood circulation to ischemic heart muscle. Naturally, in overdose, they can be cardiotoxic, prolonging heart rhythms and increasing myocardial irritability.

New research has also revealed compelling evidence of a link between long-term use of anticholinergic medications like TCAs and dementia.[25] Although many studies have investigated this link, this was the first study to use a long-term approach (over seven years) to find that dementias associated with anticholinergics may not be reversible even years after drug use stops.[26] Anticholinergic drugs block the action of acetylcholine, which transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory.

Discontinuation

[edit]

Antidepressants in general may produce withdrawal. However, since the term "withdrawal" has been linked to addiction to recreational drugs like opioids, the medical profession and pharmaceutical public relations prefer that a different term be used, hence "discontinuation syndrome."[27] Discontinuation symptoms can be managed by a gradual reduction in dosage over a period of weeks or months to minimise symptoms.[28] In tricyclics, discontinuation syndrome symptoms include anxiety, insomnia, cholinergic rebound, headache, nausea, malaise, or motor disturbance.[29]

Overdose

[edit]
Main article: Tricyclic antidepressant overdose

TCA overdose is a significant cause of fatal drug poisoning. The severe morbidity and mortality associated with these drugs is well documented due to their cardiovascular and neurological toxicity. Additionally, it is a serious problem in the pediatric population due to their inherent toxicity[30] and the availability of these in the home when prescribed for bed-wetting and depression. In the event of a known or suspected overdose, medical assistance should be sought immediately.

A number of treatments are effective in a TCA overdose.

An overdose on TCA is especially fatal as it is rapidly absorbed from the GI tract in the alkaline conditions of the small intestines. As a result, toxicity often becomes apparent in the first hour after an overdose. However, symptoms may take several hours to appear if a mixed overdose has caused delayed gastric emptying.

Many of the initial signs are those associated to the anticholinergic effects of TCAs such as dry mouth, blurred vision, urinary retention, constipation, dizziness, and emesis (or vomiting). Due to the location of norepinephrine receptors all over the body, many physical signs are also associated with a TCA overdose:[31]

  1. Anticholinergic effects: altered mental status (e.g., agitation, confusion, lethargy, etc.), resting sinus tachycardia, dry mouth, mydriasis, blurred vision, fever
  2. Cardiac effects: hypertension (early and transient, should not be treated), tachycardia, orthostasis and hypotension, arrhythmias (including ventricular tachycardia and ventricular fibrillation, most serious consequence), ECG changes (prolonged QRS, QT, and PR intervals)
  3. CNS effects: syncope, seizure, coma, myoclonus, hyperreflexia, convulsions, drowsiness
  4. Pulmonary effects: hypoventilation resulting from CNS depression[32]
  5. Gastrointestinal effects: decreased or absent bowel sounds, constipation

Treatment of TCA overdose depends on severity of symptoms:

Initially, gastric decontamination of the patient is achieved by administering, either orally or via a nasogastric tube, activated charcoal pre-mixed with water, which adsorbs the drug in the gastrointestinal tract (most useful if given within 2 hours of drug ingestion). Other decontamination methods such as stomach pumps, gastric lavage, whole bowel irrigation, or (ipecac induced) emesis, are not  recommended in TCA poisoning.

If there is metabolic acidosis, intravenous infusion of sodium bicarbonate is recommended by Toxbase.org, the UK and Ireland poisons advice database (TCAs are protein bound and become less bound in more acidic conditions, so by reversing the acidosis, protein binding increases and bioavailability thus decreases – the sodium load may also help to reverse the Na+ channel blocking effects of the TCA).

Interactions

[edit]

The TCAs are highly metabolised by the cytochrome P450 (CYP) hepatic enzymes. Drugs that inhibit cytochrome P450 (for example cimetidine, methylphenidate, fluoxetine, antipsychotics, and calcium channel blockers) may produce decreases in the TCAs' metabolism, leading to increases in their blood concentrations and accompanying toxicity.[33] Drugs that prolong the QT interval including antiarrhythmics such as quinidine, the antihistamines astemizole and terfenadine, and some antipsychotics may increase the chance of ventricular dysrhythmias. TCAs may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Side effects may also be enhanced by other drugs that have antimuscarinic properties.

Pharmacology

[edit]

The majority of the TCAs act primarily as SNRIs by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), which results in an elevation of the synaptic concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission.[34][35] Notably, with the sole exception of amineptine, the TCAs have weak affinity for the dopamine transporter (DAT), and therefore have low efficacy as dopamine reuptake inhibitors (DRIs).[34] Both serotonin and norepinephrine have been highly implicated in depression and anxiety, and it has been shown that facilitation of their activity has beneficial effects on these mental disorders.[36]

In addition to their reuptake inhibition, many TCAs also have high affinity as antagonists at the 5-HT2[37] (5-HT2A[38] and 5-HT2C[38]), 5-HT6,[39] 5-HT7,[40] α1-adrenergic,[37] and NMDA receptors,[41] and as agonists at the sigma receptors[42] (σ1[42] and σ2[43]), some of which may contribute to their therapeutic efficacy, as well as their side effects.[44] The TCAs also have varying but typically high affinity for antagonising the H1[37] and H2[45][46] histamine receptors, as well as the muscarinic acetylcholine receptors.[37] As a result, they also act as potent antihistamines and anticholinergics. These properties are often beneficial in antidepressants, especially with comorbid anxiety, as it provides a sedative effect.[47]

Most, if not all, of the TCAs also potently inhibit sodium channels and L-type calcium channels, and therefore act as sodium channel blockers and calcium channel blockers, respectively.[48][49] The former property is responsible for the high mortality rate upon overdose seen with the TCAs via cardiotoxicity.[50] It may also be involved in their efficacy as analgesics, however.[51]

In summary, tricyclic antidepressants can act through NMDA antagonism, opioidergic effects, sodium, potassium and calcium channel blocking, through interfering with the reuptake of serotonin and acting as antagonists to SHAM (serotonin, histamine, alpha, muscarinic) receptors.

Binding profiles

[edit]
See also: Tetracyclic antidepressant § Binding profiles

The binding profiles of various TCAs and some metabolites in terms of their affinities (Ki, nM) for various receptors and transporters are as follows:[52]

Compound SERTTooltip Serotonin transporter NETTooltip Norepinephrine transporter DATTooltip Dopamine transporter 5-HT1A 5-HT2A 5-HT2C 5-HT6 5-HT7 α1 α2 D2 H1 H2 mAChTooltip Muscarinic acetylcholine receptor σ1 σ2
Amineptine >100,000 10,000 1,000–1,400 >100,000 74,000 ND ND ND >100,000 >100,000 >100,000 ≥13,000 ND >100,000 ND ND
Amitriptyline 2.8–4.3 19–35 3,250 ≥450 18–23 4.0 65–141 93–123 4.4–24 114–690 196–1,460 0.5–1.1 66 9.6 300 ND
Amoxapine 58 16 4,310 ND 0.5 2.0 6.0–50 41 50 2,600 3.6–160 7.9–25 ND 1,000 ND ND
Butriptyline ≥1,360 5,100 3,940 7,000 380 ND ND ND 570 4,800 ND 1.1 ND 35 ND ND
Clomipramine 0.14–0.28 38–54 ≥2,190 ≥7,000 27–36 65 54 127 3.2–38 ≥535 78–190 13–31 209 37 546 ND
Desipramine 18–163 0.63–3.5 3,190 ≥6,400 115–350 244–748 ND >1,000 23–130 ≥1,379 3,400 60–110 1,550 66–198 ≥1,990 ≥1,610
Dibenzepin ND ND >10,000 >10,000 ≥1,500 ND ND ND >10,000 >10,000 >10,000 23 1,950 1,750 ND ND
Dosulepin 8.6–78 46–70 5,310 4,000 152 ND ND ND 419 2,400 ND 3.6–4.0 ND 25–26 ND ND
Doxepin 68–210 13–58 ≥4,600 276 11–27 8.8–200 136 ND 24 28–1,270 360 0.09–1.23 174 23–80 ND ND
Imipramine 1.3–1.4 20–37 8,500 ≥5,800 80–150 120 190–209 >1,000 32 3,100 620–726 7.6–37 550 46 332–520 327–2,100
Iprindole ≥1,620 1,260 6,530 2,800 217–280 206 ND ND 2,300 8,600 6,300 100–130 200–8,300 2,100 >10,000 ND
Lofepramine 70 5.4 >10,000 4,600 200 ND ND ND 100 2,700 2,000 245–360 4,270 67 2,520 ND
Maprotiline 5,800 11–12 1,000 ND 51 122 ND 50 90 9,400 350–665 0.79–2.0 776 570 ND ND
Norclomipramine 40 0.45 2,100 19,000 130 ND ND ND 190 1,800 1,200 450 ND 92 ND ND
Northiaden 192 25 2,539 2,623 141 ND ND ND 950 ND ND 25 ND 110 ND ND
Nortriptyline 15–18 1.8–4.4 1,140 294 5.0–41 8.5 148 ND 55 2,030 2,570 3.0–15 646 37 2,000 ND
Opipramol ≥2,200 ≥700 ≥3,000 >10,000 120 ND ND ND 200 6,100 120–300 6.0 4,470 3,300 0.2–50 110
Protriptyline 19.6 1.41 2,100 3,800 70 ND ND ND 130 6,600 2,300 7.2–25 398 25 ND ND
Tianeptine >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000 >10,000
Trimipramine 149–2,110 ≥2,450 ≥3,780 8,000 32 537 ND ND 24 680 143–210 0.27–1.5 41 58 ND ND
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. For assay species and references, see the individual drug articles. Most but not all values are for human proteins.

With the exception of the sigma receptors, the TCAs act as antagonists or inverse agonists of the receptors and as inhibitors of the transporters. Tianeptine is included in this list due to it technically being a TCA, but with a vastly different pharmacology.

Therapeutic levels of TCAs are generally in the range of about 100 to 300 ng/mL, or 350 to 1,100 nM.[53] Plasma protein binding is generally 90% or greater.[53]

Chemistry

[edit]

There are two major groups of TCAs in terms of chemical structure, which most, but not all, TCAs fall into.[54][55][56] The groupings are based on the tricyclic ring system.[54][55][56] They are the dibenzazepines (imipramine, desipramine, clomipramine, trimipramine, lofepramine) and the dibenzocycloheptadienes (amitriptyline, nortriptyline, protriptyline, butriptyline).[54][55] Minor TCA groups based on ring system include the dibenzoxepins (doxepin), the dibenzothiepines (dosulepin), and the dibenzoxazepines (amoxapine).[54][55]

In addition to classification based on the ring system, TCAs can also be usefully grouped based on the number of substitutions of the side chain amine.[56][57] These groups include the tertiary amines (imipramine, clomipramine, trimipramine, amitriptyline, butriptyline, doxepin, dosulepin) and the secondary amines (desipramine, nortriptyline, protriptyline).[56][57] Lofepramine is technically a tertiary amine, but acts largely as a prodrug of desipramine, a secondary amine, and hence is more similar in profile to the secondary amines than to the tertiary amines.[57] Amoxapine does not have the TCA side chain and hence is neither a tertiary nor secondary amine, although it is often grouped with the secondary amines due to sharing more in common with them.[58] In 2021, a new method was developed at the Institute for Bioengineering of Catalonia for designing photochromic analogs of tricyclic drugs via (1) isosteric replacement of the two-atom bridge between the aromatic systems with an azo group and (2) opening of the central ring. The authors named the strategy "crypto-azologization".[59]

History

[edit]

The TCAs were developed amid the "explosive birth" of psychopharmacology in the early 1950s. The story begins with the synthesis of chlorpromazine in December 1950 by Rhône-Poulenc's chief chemist, Paul Charpentier, from synthetic antihistamines developed by Rhône-Poulenc in the 1940s.[60] Its psychiatric effects were first noticed at a hospital in Paris in 1952. The first widely used psychiatric drug, by 1955 it was already generating significant revenue as an antipsychotic.[61] Research chemists quickly began to explore other derivatives of chlorpromazine.

The first TCA reported for the treatment of depression was imipramine, a dibenzazepine analogue of chlorpromazine code-named G22355. It was not originally targeted for the treatment of depression. The drug's tendency to induce manic effects was "later described as 'in some patients, quite disastrous'". The paradoxical observation of a sedative inducing mania led to testing with depressed patients. The first trial of imipramine took place in 1955 and the first report of antidepressant effects was published by Swiss psychiatrist Roland Kuhn in 1957.[62] Some testing of Geigy's imipramine, then known as Tofranil, took place at the Münsterlingen Hospital near Konstanz.[61] Geigy later became Ciba-Geigy and eventually Novartis.

Dibenzazepine derivatives are described in U.S. patent 3,074,931 issued 1963-01-22 by assignment to Smith Kline & French Laboratories. The compounds described share a tricyclic backbone different from the backbone of the TCA amitriptyline.

Merck introduced the second member of the TCA family, amitriptyline (Elavil), in 1961.[61] This compound has a different three-ring structure than imipramine.

Society and culture

[edit]

Recreational use

[edit]

A very small number of cases involving non-medical use of antidepressants have been reported over the past 30 years.[63] According to the US government classification of psychiatric medications, TCAs are "non-abusable"[64] and generally have low misuse potential.[65] Nonetheless, due to their atypical mechanism of action, amineptine and tianeptine (dopamine reuptake inhibition and μ-opioid receptor agonism, respectively) are the two TCAs with the highest addiction and misuse potential. Several cases of the misuse[66] of amitriptyline alone[67][68] or together with methadone[66][69] or in other drug dependent patients[70][71] and of dosulepin with alcohol[72] or in methadone patients[73] have been reported.

List of TCAs

[edit]

Those that preferentially inhibit the reuptake of serotonin (by at least 10-fold over norepinephrine) include:

Those that preferentially inhibit the reuptake of norepinephrine (by at least 10-fold over serotonin) include:

Whereas either fairly balanced reuptake inhibitors of serotonin and norepinephrine or unspecified inhibitors include:

And the following are TCAs that act via main mechanisms other than serotonin or norepinephrine reuptake inhibition:

Legend:

  • † indicates products which have been withdrawn from the market worldwide.
  • ‡ indicates products which are not available in any country in which English is an official language.
  • § indicates products which are not available in the United States, but are available in other English-speaking countries such as Australia, Canada, United Kingdom, etc.
  • Bolded names indicates products which are available in at least three countries in which English is an official language.

See also

[edit]

References

[edit]
  1. ^ Carson VB (2000). Mental health nursing: the nurse-patient journey W.B. Saunders. ISBN 978-0-7216-8053-8. pp. 423
  2. ^ Trindade E, Menon D, Topfer LA, Coloma C (November 1998). "Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis". CMAJ. 159 (10): 1245–1252. PMC 1229819. PMID 9861221.
  3. ^ Shiel WC, ed. (n.d.). "Attention-Deficit/Hyperactivity Disorder: Nonstimulant Therapy (Strattera) and Other ADHD Drugs". MedicineNet (Web page). Archived from the original on 23 March 2005.
  4. ^ Paumier KL, Siderowf AD, Auinger P, Oakes D, Madhavan L, Espay AJ, et al. (June 2012). "Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson's disease" (PDF). Movement Disorders. 27 (7): 880–887. doi:10.1002/mds.24978. PMID 22555881.
  5. ^ Caldwell PH, Sureshkumar P, Wong WC (January 2016). Glazener CM (ed.). "Tricyclic and related drugs for nocturnal enuresis in children". The Cochrane Database of Systematic Reviews. 2016 (1): CD002117. doi:10.1002/14651858.CD002117.pub2. PMC 8741207. PMID 26789925.
  6. ^ Moraczewski J, Awosika AO, Aedma KK (17 August 2023). "Tricyclic antidepressants". StatPearls. Treasure Island, Florida: StatPearls Publishing. PMID 32491723. Retrieved 8 October 2023.
  7. ^ Gillman PK (July 2007). "Tricyclic antidepressant pharmacology and therapeutic drug interactions updated". British Journal of Pharmacology. 151 (6): 737–748. doi:10.1038/sj.bjp.0707253. PMC 2014120. PMID 17471183.
  8. ^ Mitchell PB, Mitchell MS (September 1994). "The management of depression. Part 2. The place of the new antidepressants". Australian Family Physician. 23 (9): 1771–3, 1776–1781. PMID 7980178.
  9. ^ Broquet KE (September 1999). "Status of treatment of depression". Southern Medical Journal. 92 (9): 846–856. doi:10.1097/00007611-199909000-00001. PMID 10498158.
  10. ^ Teicher MH, Glod CA, Cole JO (March 1993). "Antidepressant drugs and the emergence of suicidal tendencies". Drug Safety. 8 (3): 186–212. doi:10.2165/00002018-199308030-00002. PMID 8452661. S2CID 36366654.
  11. ^ a b c d e f g h Kamp CB, Petersen JJ, Faltermeier P, Juul S, Siddiqui F, Barbateskovic M, Kristensen AT, Moncrieff J, Horowitz MA, Hengartner MP, Kirsch I, Gluud C, Jakobsen JC (2024). "Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis". BMJ Mental Health. 27 (1): e300730. doi:10.1136/bmjment-2023-300730. ISSN 2755-9734. PMC 10806869. PMID 39093721.
  12. ^ Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR (April 2018). "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis". Lancet. 391 (10128): 1357–1366. doi:10.1016/S0140-6736(17)32802-7. PMC 5889788. PMID 29477251.
  13. ^ Biederman J, Baldessarini RJ, Wright V, Knee D, Harmatz JS (September 1989). "A double-blind placebo controlled study of desipramine in the treatment of ADD: I. Efficacy". Journal of the American Academy of Child and Adolescent Psychiatry. 28 (5): 777–784. doi:10.1097/00004583-198909000-00022. PMID 2676967.
  14. ^ Blum K, Chen AL, Braverman ER, Comings DE, Chen TJ, Arcuri V, et al. (October 2008). "Attention-deficit-hyperactivity disorder and reward deficiency syndrome". Neuropsychiatric Disease and Treatment. 4 (5): 893–918. doi:10.2147/NDT.S2627. PMC 2626918. PMID 19183781.
  15. ^ Biederman J, Spencer T (November 1999). "Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder". Biological Psychiatry. 46 (9): 1234–1242. doi:10.1016/S0006-3223(99)00192-4. PMID 10560028. S2CID 45497168.
  16. ^ Popper CW (1997). "Antidepressants in the treatment of attention-deficit/hyperactivity disorder". The Journal of Clinical Psychiatry. 58 (Suppl 14): 14–29, discussion 30–1. PMID 9418743.
  17. ^ Micó JA, Ardid D, Berrocoso E, Eschalier A (July 2006). "Antidepressants and pain". Trends in Pharmacological Sciences. 27 (7): 348–354. doi:10.1016/j.tips.2006.05.004. PMID 16762426.
  18. ^ McQuay HJ, Tramèr M, Nye BA, Carroll D, Wiffen PJ, Moore RA (December 1996). "A systematic review of antidepressants in neuropathic pain". Pain. 68 (2–3): 217–227. doi:10.1016/S0304-3959(96)03140-5. PMID 9121808. S2CID 25124663.
  19. ^ Botney M, Fields HL (February 1983). "Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system". Annals of Neurology. 13 (2): 160–164. doi:10.1002/ana.410130209. PMID 6219612. S2CID 40631429.
  20. ^ Benbouzid M, Gavériaux-Ruff C, Yalcin I, Waltisperger E, Tessier LH, Muller A, et al. (March 2008). "Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia". Biological Psychiatry. 63 (6): 633–636. doi:10.1016/j.biopsych.2007.06.016. PMID 17693391. S2CID 22957748.
  21. ^ de Gandarias JM, Echevarria E, Acebes I, Silio M, Casis L (July 1998). "Effects of imipramine administration on mu-opioid receptor immunostaining in the rat forebrain". Arzneimittel-Forschung. 48 (7): 717–719. PMID 9706370.
  22. ^ Jackson JL, Shimeall W, Sessums L, et al. (2010). "Tricyclic antidepressants and headaches: systematic review and meta-analysis". BMJ. 341: c5222. doi:10.1136/bmj.c5222. PMC 2958257. PMID 20961988.
  23. ^ Gelder MG, Mayou R, Geddes J (2005). Psychiatry (3rd ed.). Oxford University Press. p. 243. ISBN 978-0-19-852863-0.
  24. ^ Chabria SB (July 2006). "Rhabdomyolysis: a manifestation of cyclobenzaprine toxicity". Journal of Occupational Medicine and Toxicology. 1: 16. doi:10.1186/1745-6673-1-16. PMC 1540431. PMID 16846511.
  25. ^ Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA Internal Medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. PMC 4358759. PMID 25621434.
  26. ^ Fox C (30 April 2015). "Strong Link Found Between Dementia, Common Anticholinergic Drugs". Drug Discovery & Development. Rockaway, New Jersey: Advantage Business Media. ISSN 1524-783X. OCLC 60617296. Archived from the original on 2 May 2015. summarizing Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB (1 March 2015). "Cumulative use of strong anticholinergics and incident dementia". JAMA Internal Medicine. 175 (3). American Medical Association: 401–407. doi:10.1001/jamainternmed.2014.7663. ISSN 2168-6106. PMC 4358759.
  27. ^ Shelton RC (2006). "The nature of the discontinuation syndrome associated with antidepressant drugs". The Journal of Clinical Psychiatry. 67 (Suppl 4): 3–7. PMID 16683856.
  28. ^ van Broekhoven F, Kan CC, Zitman FG (June 2002). "Dependence potential of antidepressants compared to benzodiazepines". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 26 (5): 939–943. doi:10.1016/S0278-5846(02)00209-9. PMID 12369270. S2CID 14286356.
  29. ^ Kunze K. "Somatic therapies in psychiatry". Des Moines University Psychiatry Class.[permanent dead link‍][better source needed]
  30. ^ Rosenbaum TG, Kou M (February 2005). "Are one or two dangerous? Tricyclic antidepressant exposure in toddlers". The Journal of Emergency Medicine. 28 (2): 169–174. doi:10.1016/j.jemermed.2004.08.018. PMID 15707813.
  31. ^ California Poison Control 1-800-876-4766
  32. ^ Crome P (1 August 1986). "Poisoning due to tricyclic antidepressant overdosage: Clinical presentation and treatment". Medical Toxicology. 1 (4): 261–285. doi:10.1007/BF03259843. PMID 3537621.
  33. ^ Preskorn SH (1996). "Why Are CYP Enzymes Important When Considering SSRIs?". Clinical pharmacology of serotonin selective reuptake inhibitors. Caddo, Oklahoma: Professional Communications. ISBN 978-1-884735-08-0. OCLC 41113507.
  34. ^ a b Tatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European Journal of Pharmacology. 340 (2–3): 249–258. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821.
  35. ^ Gillman PK (July 2007). "Tricyclic antidepressant pharmacology and therapeutic drug interactions updated". British Journal of Pharmacology. 151 (6): 737–748. doi:10.1038/sj.bjp.0707253. PMC 2014120. PMID 17471183.
  36. ^ Rénéric JP, Lucki I (March 1998). "Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test". Psychopharmacology. 136 (2): 190–197. doi:10.1007/s002130050555. PMID 9551776. S2CID 8093564.
  37. ^ a b c d Cusack B, Nelson A, Richelson E (May 1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds". Psychopharmacology. 114 (4): 559–565. doi:10.1007/BF02244985. PMID 7855217. S2CID 21236268.
  38. ^ a b Sánchez C, Hyttel J (August 1999). "Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding". Cellular and Molecular Neurobiology. 19 (4): 467–489. doi:10.1023/A:1006986824213. PMID 10379421. S2CID 19490821.
  39. ^ Branchek TA, Blackburn TP (2000). "5-ht6 receptors as emerging targets for drug discovery". Annual Review of Pharmacology and Toxicology. 40: 319–334. doi:10.1146/annurev.pharmtox.40.1.319. PMID 10836139.
  40. ^ Stam NJ, Roesink C, Dijcks F, Garritsen A, van Herpen A, Olijve W (August 1997). "Human serotonin 5-HT7 receptor: cloning and pharmacological characterisation of two receptor variants". FEBS Letters. 413 (3): 489–494. Bibcode:1997FEBSL.413..489S. doi:10.1016/S0014-5793(97)00964-2. PMID 9303561. S2CID 7965330.
  41. ^ Sills MA, Loo PS (July 1989). "Tricyclic antidepressants and dextromethorphan bind with higher affinity to the phencyclidine receptor in the absence of magnesium and L-glutamate" (PDF). Molecular Pharmacology. 36 (1): 160–165. ISSN 0026-895X. PMID 2568580.
  42. ^ a b Narita N, Hashimoto K, Tomitaka S, Minabe Y (June 1996). "Interactions of selective serotonin reuptake inhibitors with subtypes of sigma receptors in rat brain". European Journal of Pharmacology. 307 (1): 117–119. doi:10.1016/0014-2999(96)00254-3. PMID 8831113.
  43. ^ Volz HP, Stoll KD (November 2004). "Clinical trials with sigma ligands". Pharmacopsychiatry. 37 (Suppl 3): S214–S220. doi:10.1055/s-2004-832680. PMID 15547788. S2CID 260238757.
  44. ^ Guzman F (29 July 2011) [28 April 2010]. "Differences between tricyclic antidepressants and SNRIs mechanism of action". Pharmacology Corner. Mendoza, Argentina: Author.
  45. ^ Green JP, Maayani S (September 1977). "Tricyclic antidepressant drugs block histamine H2 receptor in brain". Nature. 269 (5624): 163–165. Bibcode:1977Natur.269..163G. doi:10.1038/269163a0. PMID 20581. S2CID 1153522.
  46. ^ Tsai BS, Yellin TO (November 1984). "Differences in the interaction of histamine H2 receptor antagonists and tricyclic antidepressants with adenylate cyclase from guinea pig gastric mucosa". Biochemical Pharmacology. 33 (22): 3621–3625. doi:10.1016/0006-2952(84)90147-3. PMID 6150708.
  47. ^ Uher R, Farmer A, Henigsberg N, Rietschel M, Mors O, Maier W, et al. (September 2009). "Adverse reactions to antidepressants" (PDF). The British Journal of Psychiatry. 195 (3): 202–210. doi:10.1192/bjp.bp.108.061960. PMID 19721108.
  48. ^ Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch C (January 1998). "Inhibition of neuronal Na+ channels by antidepressant drugs". The Journal of Pharmacology and Experimental Therapeutics. 284 (1): 208–214. PMID 9435180. Archived from the original on 29 August 2021. Retrieved 20 July 2009.
  49. ^ Zahradník I, Minarovic I, Zahradníková A (March 2008). "Inhibition of the cardiac L-type calcium channel current by antidepressant drugs". The Journal of Pharmacology and Experimental Therapeutics. 324 (3): 977–984. CiteSeerX 10.1.1.1030.7935. doi:10.1124/jpet.107.132456. PMID 18048694. S2CID 24777.
  50. ^ Harrigan RA, Brady WJ (July 1999). "ECG abnormalities in tricyclic antidepressant ingestion". The American Journal of Emergency Medicine. 17 (4): 387–393. doi:10.1016/S0735-6757(99)90094-3. PMID 10452441.
  51. ^ Brian E. Cairns (1 September 2009). Peripheral Receptor Targets for Analgesia: Novel Approaches to Pain Management. John Wiley & Sons. pp. 66–68. ISBN 978-0-470-52221-9.
  52. ^ Roth, BL, Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  53. ^ a b Nelson JC (2009). "Tricyclic and tetracyclic drugs". In Schatzberg AF, Nemeroff CB (eds.). The American Psychiatric Publishing textbook of psychopharmacology (4th ed.). Arlington, Virginia: American Psychiatric Publishing. pp. 263–287, at pp. 267–271. ISBN 978-1-58562-309-9.
  54. ^ a b c d K. Ghose (11 November 2013). Antidepressants for Elderly People. Springer. pp. 182–. ISBN 978-1-4899-3436-9.
  55. ^ a b c d J. K. Aronson (2009). Meyler's Side Effects of Psychiatric Drugs. Elsevier. pp. 7–. ISBN 978-0-444-53266-4.
  56. ^ a b c d Patricia K. Anthony (2002). Pharmacology Secrets. Elsevier Health Sciences. pp. 39–. ISBN 978-1-56053-470-9.
  57. ^ a b c Cowen P, Harrison P, Burns T (9 August 2012). Shorter Oxford Textbook of Psychiatry. Oxford University Press. pp. 532–. ISBN 978-0-19-162675-3.
  58. ^ Schatzberg AF, Nemeroff CB, eds. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology (5th ed.). American Psychiatric Publishing. pp. 306–. ISBN 978-1-58562-523-9.
  59. ^ Riefolo F, Sortino R, Matera C, Claro E, Preda B, Vitiello S, et al. (July 2021). "Rational Design of Photochromic Analogues of Tricyclic Drugs" (PDF). Journal of Medicinal Chemistry. 64 (13): 9259–9270. doi:10.1021/acs.jmedchem.1c00504. hdl:2434/855420. PMID 34160229. hdl:2445/178992 Zenodo: 6088090.
  60. ^ Cunningham Owens DG (11 March 1999). "The background" (PDF). A guide to the extrapyramidal side effects of antipsychotic drugs. Cambridge, UK: Cambridge University Press. pp. 1–17, at p. 4. doi:10.1017/cbo9780511544163.002. ISBN 978-0-521-63353-6.
  61. ^ a b c Rose N (2004). "Becoming Neurochemical Selves" (PDF). In Stehr N (ed.). Biotechnology: Between Commerce and Civil Society. New Brunswick, New Jersey: Transaction Publishers. pp. 89–128, at pp. 90–91. doi:10.4324/9781351323048. hdl:10822/994593. ISBN 978-0-7658-0224-8.
  62. ^ Cunningham Owens DG (11 March 1999). "The background" (PDF). A guide to the extrapyramidal side effects of antipsychotic drugs. Cambridge, UK: Cambridge University Press. pp. 1–17, at p. 3. doi:10.1017/cbo9780511544163.002. ISBN 978-0-521-63353-6.
  63. ^ Wills S (2005). Drugs of abuse (2nd ed.). London: Pharmaceutical Press. p. 213. ISBN 978-0-85369-582-0.
  64. ^ Center for Substance Abuse Treatment (1995). "Mental health and counseling needs of HIV-infected AOD abusers". Treatment for HIV-infected alcohol and other drug abusers. Treatment Improvement Protocol (TIP) series. Vol. 15. Rockville, Maryland: Substance Abuse and Mental Health Services Administration. Exhibit 4-3 Abuse Potential of Common Psychiatric Medications. PMID 22514820.
  65. ^ Center for Substance Abuse Treatment (2000). "Mental health treatment". Substance abuse treatment for persons with HIV/AIDS. Treatment Improvement Protocol (TIP) series. Vol. 37. Rockville, Maryland: Substance Abuse and Mental Health Services Administration. Figure 3-4: Abuse potential of common psychiatric medications. PMID 22514843. Republished without revision in Center for Substance Abuse Treatment (2014). Substance abuse treatment for persons with HIV/AIDS (PDF). Treatment Improvement Protocol (TIP) series. Vol. 37. Rockville, Maryland: Substance Abuse and Mental Health Services Administration. p. 83-84.
  66. ^ a b Wills S (2005). Drugs of abuse (2nd ed.). London: Pharmaceutical Press. pp. 215–216. ISBN 978-0-85369-582-0.
  67. ^ Wohlreich MM, Welch W (1993). "Amitriptyline abuse presenting as acute toxicity". Psychosomatics. 34 (2): 191–193. doi:10.1016/S0033-3182(93)71918-0. PMID 8456167. The patient denied any alcohol or substance abuse, and no signs of withdrawal were noted in the hospital...On examination, Ms. B. denied suicidal ideation or intent but did admit to taking over 800 mg of amitriptyline per day for the past 3 years after being started on the drug for depression. She clearly described a euphoria associated with amitriptyline, noting that it gave her a "buzz" and that she felt "numbed up" and calm about 30 minutes after ingestion. The patient expressed fears of being addicted to the amitriptyline and desired inpatient hospitalization for medication adjustment and education.
  68. ^ Singh GP, Kaur P, Bhatia S (June 2004). "Dothiepin dependence syndrome". Indian Journal of Medical Sciences. 58 (6): 253–254. PMID 15226578.
  69. ^ Cohen MJ, Hanbury R, Stimmel B (September 1978). "Abuse of amitriptyline". JAMA. 240 (13): 1372–1373. doi:10.1001/jama.240.13.1372. PMID 682328.
  70. ^ Delisle JD (October 1990). "A case of amitriptyline abuse". The American Journal of Psychiatry. 147 (10): 1377–1378. doi:10.1176/ajp.147.10.1377b. PMID 2400006. Ms. A, a 24-year-old abuser of alcohol and cannabis, consulted her family physician because of anxiety, depression, and insomnia. Unaware of her drug abuse, he prescribed amitriptyline, 200 mg. About 30 minutes after taking each dose, she would experience relief from her symptoms that lasted about 2 hours. By increasing the dose, she found she could intensify these effects and prolong them for up to several hours. Her "high" consisted of feelings of relaxation, giddiness, and contentment.Frequently, this progressed to incoordination, slurred speech, and confusion. Sometimes she would forget how much she had taken and ingest up to 2 g.
  71. ^ Sein Anand J, Chodorowski Z, Habrat B (2005). "Recreational amitriptyline abuse" (PDF). Przegląd Lekarski (Case report). 62 (6). Kraków: Wydawnictwo Przegląd Lekarski: 397–398. ISSN 0033-2240. OCLC 1424404558. PMID 16225078. S2CID 27766729. Archived from the original (PDF) on 2 December 2023.
  72. ^ Lepping P, Menkes DB (July 2007). "Abuse of dosulepin to induce mania". Addiction. 102 (7): 1166–1167. doi:10.1111/j.1360-0443.2007.01828.x. PMID 17567406.
  73. ^ Dorman A, Talbot D, Byrne P, O'Connor J (December 1995). "Misuse of dothiepin". BMJ. 311 (7018): 1502. doi:10.1136/bmj.311.7018.1502b. PMC 2543748. PMID 8520352.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Tricyclic_antidepressant&oldid=1260447391"