An anxiolytic (also antipanic or antianxiety agent)[1] is a drug that inhibits anxiety. This effect is in contrast to anxiogenic agents, which increase anxiety. Together these categories of psychoactive compounds may be referred to as anxiotropic compounds. Some recreational drugs like alcoholic beverages (which contain ethanol) induce anxiolysis. Anxiolytic medications have been used for the treatment of anxiety and its related psychological and physical symptoms. Anxiolytics have been shown to be useful in the treatment of anxiety disorders.
Beta-receptor blockers such as propranolol and oxprenolol, although not anxiolytics, can be used to combat the somatic symptoms of anxiety.
Anxiolytics are also known as minor tranquilizers.[2] The term is less common in modern texts, and was originally derived from a dichotomy with major tranquilizers, also known as neuroleptics or antipsychotics.[citation needed]
Contents
- 1 Types of anxiolytics/anti-anxiety drugs
- 1.1 Medications
- 1.1.1 Benzodiazepines
- 1.1.2 Serotonergic antidepressants
- 1.1.3 Adaptol
- 1.1.4 Afobazole
- 1.1.5 Selank
- 1.1.6 Bromantane
- 1.1.7 Tenoten
- 1.1.8 Mexidol
- 1.1.9 Azapirones
- 1.1.10 Barbiturates
- 1.1.11 Hydroxyzine
- 1.1.12 Pregabalin
- 1.1.13 Validol
- 1.1.14 Herbal treatments
- 1.2 Over-the-counter pharmaceutical drugs
- 1.3 Future drugs
- 1.4 Common drugs
- 1.4.1 Alcohol
- 1.4.2 Inhalants
- 2 Alternatives to medication
- 3 See also
- 4 References
Types of anxiolytics/anti-anxiety drugs[edit]
Medications[edit]
Benzodiazepines[edit]
Main article: Benzodiazepine
Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety. Benzodiazepines may also be indicated to cover the latent periods associated with the medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide variety of conditions and symptoms and are usually a first choice when short-term CNS sedation is needed. Longer-term uses include treatment for severe anxiety. There is a risk of a benzodiazepine withdrawal and rebound syndrome after continuous usage for longer than two weeks, and tolerance and dependence may occur if patients stay under this treatment for longer.[3] There is also the added problem of the accumulation of drug metabolites and adverse effects.[4] Benzodiazepines include:
- Alprazolam (Xanax)
- Chlordiazepoxide (Librium)
- Clonazepam (Klonopin, Rivotril)
- Diazepam (Valium)
- Etizolam (Etilaam) (Actually a benzodiazepine structural analog where the benzene ring has been replaced by a thiophene ring.)
- Lorazepam (Ativan)
- Oxazepam (Serax)
Benzodiazepines exert their anxiolytic properties at moderate dosage. At higher dosage hypnotic properties occur.[5]
- Tofisopam (Emandaxin and Grandaxin) is a drug that is a benzodiazepine derivative. Like other benzodiazepines, it possesses anxiolytic properties, but, unlike other benzodiazepines, it does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing, or amnestic properties.
Serotonergic antidepressants[edit]
Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor[6] (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. SSRIs are primarily classified as antidepressants and typically higher dosages are required to be effective against anxiety disorders than to be effective against depression; nevertheless, most SSRIs have anxiolytic properties. They can, however, be anxiogenic early on in the course of treatment due to negative feedback through the serotonergic autoreceptors. For this reason in some individuals a low dose concurrent benzodiazepine therapy might be beneficial during the early stages of serotonergic therapy to counteract the initial anxiogenic effects current serotonergics antidepressants have.
Older tricyclic antidepressants (TCAs) are anxiolytic too; however, their side effects are often more severe in nature. Examples include imipramine, doxepin, amitriptyline, and the unrelated trazodone. Monoamine oxidase inhibitors (MAOIs) are very effective for anxiety, but due to drug dangers, are rarely prescribed. Examples include: phenelzine and tranylcypromine.
Adaptol[edit]
Adaptol (Mebicarum / Mebicar) is an anxiolytic produced in Latvia and used in Eastern Europe. Mebicar has an effect on the structure of limbic-reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, increases the brain serotonin level, and does not elicit cholinolytic action.
Afobazole[edit]
Afobazole is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions, making it more selective in action than many currently used drugs for this application. Its mechanism of action remains poorly defined however, with GABAergic, NGF and BDNF release promoting, MT1 receptor antagonism, MT3 receptor antagonism, and sigma agonism all thought to have some involvement. Clinical trials have shown afobazole to be well tolerated and reasonably effective for the treatment of anxiety, although it has yet to be introduced into widespread clinical use outside of Russia. The compound has not been evaluated by the FDA. It is unscheduled in the US and is legal to import by private citizens for personal use.
Selank[edit]
Selank (Russian: Cеланк) is a nootropic, anxiolytic peptide based drug developed by the Institute of Molecular Genetics of the Russian academy of sciences. Selank is a heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It is a synthetic analogue of a human tetrapeptide tuftsin. As such, it mimics many of its effects. It has been shown to modulate the expression of Interleukin-6 (IL-6) and affect the balance of T helper cell cytokines. It has been shown to influence the concentration of monoamine neurotransmitters and induce metabolism of serotonin. There is evidence that it may also modulate the expression of Brain-derived neurotropic factor (BDNF) in rats.
Bromantane[edit]
Bromantane is a stimulant drug with anxiolytic properties developed in Russia during the late 1980s, which acts mainly by inhibiting the reuptake of both dopamine and serotonin in the brain, although it also has anticholinergic effects at very high doses. Study results suggest that the combination of psychostimulant and anxiolytic actions in the spectrum of psychotropic activity of bromantane is effective in treating asthenic disorders compared to placebo. The absence of "withdrawal syndrome" demonstrated a lack of addictive potential in this drug. It is considered novel having both stimulant and anti-anxiety properties.
Tenoten[edit]
Tenoten is a Russian anxiolytic and antidepressant based on antibodies to brain-specific protein S-100B. S100 proteins are small calcium-binding proteins interacting with numerous intra- and extra cellular targets involved in diverse physiological functions. In particular, S100 proteins may be involved in the regulation of anxiety-related behavior
Mexidol[edit]
Mexidol (Emoxypine) is an antioxidant that is useful as an anxiolytic medication with few side effects (i.e. no sedation, impairment, tolerance or addition potential) compared to benzodiazepines. Its chemical structure resembles that of pyridoxine (a type of vitamin B6).
Azapirones[edit]
Azapirones are a class of 5-HT1A receptor agonists. Currently approved azapirones include buspirone (Buspar) and tandospirone (Sediel). Gepirone (Ariza, Variza) is also in clinical development.
Barbiturates[edit]
Main article: Barbiturate
Barbiturates exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and addiction is high. Many experts consider these drugs obsolete for treating anxiety but valuable for the short-term treatment of severe insomnia, though only after benzodiazepines or non-benzodiazepines have failed. They are rarely prescribed any more.
Hydroxyzine[edit]
Hydroxyzine (Atarax) is an old antihistamine originally approved for clinical use by the FDA in 1956. It possesses anxiolytic properties in addition to its antihistamine properties and is also licensed for the treatment of anxiety and tension. It is also used for its sedative properties as a premed before anesthesia or to induce sedation after anesthesia.[7] It has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder, while producing fewer side-effects.[8]
Pregabalin[edit]
Pregabalin's therapeutic effect appears after 1 week of use and is similar in effectiveness to lorazepam, alprazolam, and venlafaxine, but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance, and, in addition, unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment; it also has a low potential for abuse and dependence and may be preferred over the benzodiazepines for these reasons.[9][10]
Validol[edit]
Sublingual administration of Validol produces a sedative effect, and has moderate reflex and vascular dilative action caused by stimulation of sensory nerve receptors of the oral mucosa followed by the release of endorphins. Validol is typically administered as needed for symptom relief.[11][12][13]
Herbal treatments[edit]
Certain natural substances are reputed to have anxiolytic properties, including the following:
- Bacopa monnieri (Brahmi)
- Lactuca virosa (Opium Lettuce)
- Rhodiola rosea (Arctic Weed/Golden Root)
- Hypericum perforatum (St. John's Wort)
- Matricaria recutita (German Chamomile)
- Passiflora incarnata
- Piper methysticum (Kava)
- Sceletium tortuosum (Kanna)
- Scutellaria spp. (Skullcap)
- Scutellaria lateriflora[14]
- Valeriana officinalis (Valerian)
- Salvia splendens (Not to be confused with Salvia divinorum)
- Coriandrum sativum (Coriander)[15]
- Myristica (Nutmeg)
- Salvia elegans (Pineapple Sage)[16]
- Inositol [17] In a double-blind, controlled trial, myo-inositol (18 grams daily) was superior to fluvoxamine for decreasing the number of panic attacks and had fewer side-effects.[18]
- Cannabidiol (a cannabinoid found in marijuana)[19]
Over-the-counter pharmaceutical drugs[edit]
Picamilon is a prodrug formed by combining niacin with GABA that is able to cross the blood–brain barrier and is then hydrolyzed into GABA and niacin. It is theorized that the GABA released in this process activates GABA receptors, with potential to produce an anxiolytic response.[20][21] Picamilon is sold in the United States as a dietary supplement, while in Russia it is sold as a prescription drug.
Chlorpheniramine (Chlor-Trimeton)[22] and Diphenhydramine (Benadryl) have hypnotic and sedative effects with mild anxiolytic-like properties (off-label use). These drugs are approved by the FDA for allergies, rhinitis, and urticaria.
Melatonin has anxiolytic properties, likely mediated by the benzodiazepine/GABAergic system.[23] It has been used experimentally as an effective premedicant for general anesthesia in surgical procedures.[24]
Future drugs[edit]
Due to deficits with existing anxiolytics (either in terms of efficacy or side-effect profile), research into novel anxiolytics is active. Possible candidates for future drugs include:
- BNC210
- CL-218,872
- L-838,417
- SL-651,498
- aloradine
Common drugs[edit]
Prescription-free drugs are often poor anxiolytics and often worsen the symptoms over time[citation needed]. However, they are often used for self-medication because of their wide availability (e.g. alcoholic beverages).
Alcohol[edit]
See also: Short-term effects of alcohol
Ethanol is used as an anxiolytic, sometimes by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.[25] The British National Formulary states, "Alcohol is a poor hypnotic because its diuretic action interferes with sleep during the latter part of the night." Alcohol is also known to induce alcohol-related sleep disorders.[26]
Inhalants[edit]
See also: Inhalant abuse#Patterns of non-medical usage and Street children in Latin America#Drugs
The anxiolytic effects of solvents act as positive modulators of GABAA receptors (Bowen and colleagues 2006).[27]
Inhalants are commonly used as anxiolytics by street children in Latin America, Africa, and Asia but also by impoverished indigenous communities.
Alternatives to medication[edit]
Psychotherapeutic treatment can be an effective alternative to medication.[28] Exposure therapy is the recommended treatment for phobic anxiety disorders. Cognitive behavioral therapy (CBT) has been found to be effective treatment for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Healthcare providers can also help by educating sufferers about anxiety disorders and referring individuals to self-help resources.[29] CBT has been shown to be effective in the treatment of generalized anxiety disorder, and possibly more effective than pharmacological treatments in the long term.[30] Sometimes medication is combined with psychotherapy, but research has found that there is no benefit of combined pharmacotherapy and psychotherapy versus monotherapy.[31]
See also[edit]
- ATC code N05#N05B Anxiolytics
References[edit]
- ^ "antianxiety agent" at Dorland's Medical Dictionary
- ^ "anxiolytic (tranquilizer)". Memidex (WordNet) Dictionary/Thesaurus. Retrieved 2010-12-02.
- ^ Gelder, M, Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp236.
- ^ Lader M, Tylee A, Donoghue J (2009). "Withdrawing benzodiazepines in primary care". CNS Drugs 23 (1): 19–34. doi:10.2165/0023210-200923010-00002. PMID 19062773.
- ^ Montenegro M, Veiga H, Deslandes A (June 2005). "[Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study.]". Arq Neuropsiquiatr 63 (2B): 410–5. doi:10.1590/S0004-282X2005000300009. PMID 16059590.
- ^ Barlow, David H. Durand, V. Mark (2009). "Chapter 7: Mood Disorders and Suicide". Abnormal Psychology: An Integrative Approach (Fifth ed.). Belmont, CA: Wadsworth Cengage Learning. p. 239. ISBN 0-495-09556-7. OCLC 192055408.
- ^ medicine net. "hydroxyzine (Vistaril, Atarax)". medicinenet.com. Archived from the original on 13 May 2008. Retrieved 17 May 2008.
- ^ Llorca PM, Spadone C, Sol O (November 2002). "Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study". J Clin Psychiatry 63 (11): 1020–7. doi:10.4088/JCP.v63n1112. PMID 12444816.
- ^ Bandelow, B.; Wedekind, D.; Leon, T. (Jul 2007). "Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention.". Expert Rev Neurother 7 (7): 769–81. doi:10.1586/14737175.7.7.769. PMID 17610384.
- ^ Owen, RT. (Sep 2007). "Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety.". Drugs Today (Barc) 43 (9): 601–10. doi:10.1358/dot.2007.43.9.1133188. PMID 17940637.
- ^ The Great Soviet Encyclopedia http://encyclopedia2.thefreedictionary.com/Validol
- ^ Farmak Product Information - Validol http://farmak.ua/assets_images/drugs/instruction/en/25/Validol_Product_Information.pdf
- ^ Itop Doctor http://doctor.itop.net/DirectoryItem.aspx?DirId=1&ItemId=268
- ^ Wolfson, P; Hoffmann, DL (2003). "An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers". Alternative therapies in health and medicine 9 (2): 74–8. PMID 12652886.
- ^ Emamghoreishi M, Khasaki M, Aazam MF (2005). "Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze". Journal of Ethnopharmacology 96 (3): 365–370. doi:10.1016/j.jep.2004.06.022. PMID 15619553.
- ^ [1] Maribel Herrera-Ruiza, Yolanda García-Beltrána, Sergio Morab, Gabriela Díaz-Vélizb, Glauce S.B. Vianac, Jaime Tortorielloa, Guillermo Ramíreza, "Antidepressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans", Journal of Ethnopharmacology, Vol. 107, No. 1, pp. 53–58 (Aug. 2006)
- ^ Fux M, Levine J, Aviv A, Belmaker RH (1996). "Inositol treatment of obsessive-compulsive disorder". American Journal of Psychiatry 153 (9): 1219–1221. PMID 8780431.
- ^ Palatnik A, Frolov K, Fux M, Benjamin J (2001). "Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder". Journal of Clinical Psychopharmacology 21 (3): 335–339. doi:10.1097/00004714-200106000-00014. PMID 11386498.
- ^ Zuardi, A.W; Crippa, JA; Hallak, JE; Moreira, FA; Guimarães, FS (2006). "Cannabidiol as an antipsychotic drug" (PDF). Brazilian Journal of Medical and Biological Research 39 (4): 421–429. doi:10.1590/S0100-879X2006000400001. ISSN 0100-879X ISSN 0100-879X . PMID 16612464.
- ^ Shephard RA (June 1987). "Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action". Life Sci. 40 (25): 2429–36. doi:10.1016/0024-3205(87)90758-2. PMID 2884549.
- ^ Foster AC, Kemp JA (February 2006). "Glutamate- and GABA-based CNS therapeutics". Curr Opin Pharmacol 6 (1): 7–17. doi:10.1016/j.coph.2005.11.005. PMID 16377242.
- ^ Psychopharmacology (Berl). 2009 Oct 13;doi:10.1007/s00213-009-1695-0 http://www.anxietyinsights.info/abstract_chlorpheniramine_exerts_anxiolyticlike_effects_an.htm
- ^ Pierrefiche G, Zerbib R, Laborit H. (1993). "Anxiolytic activity of melatonin in mice: involvement of benzodiazepine receptors". Res Commun Chem Pathol Pharmacol. 82(2):131-42. PMID 7905658
- ^ Naguib M, Gottumukkala V, Goldstein PA. (2007). "Melatonin and anesthesia: a clinical perspective." J Pineal Res. 42(1):12-21. PMID 17198534
- ^ Society for Neuroscience, PDF[full citation needed]
- ^ http://pubs.niaaa.nih.gov/publications/aa41.htm
- ^ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188822/
- ^ Zwanzger, P.; Deckert, J. (Mar 2007). "[Anxiety disorders. Causes, clinical picture and treatment]". Nervenarzt 78 (3): 349–59; quiz 360. doi:10.1007/s00115-006-2202-z. PMID 17279399.
- ^ Shearer, SL. (Sep 2007). "Recent advances in the understanding and treatment of anxiety disorders". Prim Care 34 (3): 475–504, v–vi. doi:10.1016/j.pop.2007.05.002. PMID 17868756.
- ^ Gould, RA; Otto, M; Pollack, M; Yap, L (1997). "Cognitive behavioral and pharmacological treatment of generalized anxiety disorder: A preliminary meta-analysis". Behavior Therapy 28 (2): 285–305. doi:10.1016/S0005-7894(97)80048-2. Retrieved 8 November 2008.
- ^ Pull, CB. (Jan 2007). "Combined pharmacotherapy and cognitive-behavioural therapy for anxiety disorders". Curr Opin Psychiatry 20 (1): 30–5. doi:10.1097/YCO.0b013e3280115e52. PMID 17143079.
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Anxiolytics (N05B)
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GABAA
PAMs |
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non-N05B
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- Alcohols (2M2B, Ethanol (beverage), Ethchlorvynol, Methylpentynol)
- Chlormezanone
- Etifoxine
- Inhalants
- Kavalactones (Kava)
- Skullcap
- Valerenic acid (Valerian)
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Benzodiazepine
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- Adinazolam
- Alprazolam
- Bretazenil
- Bromazepam
- Camazepam
- Chlordiazepoxide
- Clobazam
- Clonazepam
- Clorazepate
- Clotiazepam
- Cloxazolam
- Diazepam#
- Ethyl Loflazepate
- Etizolam
- Fludiazepam
- Halazepam
- Imidazenil
- Ketazolam
- Lorazepam#
- Medazepam
- Nordazepam
- Oxazepam
- Pinazepam
- Prazepam
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Carbamates
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- Difebarbamate
- Emylcamate
- Febarbamate
- Mebutamate
- Meprobamate (Carisoprodol, Tybamate)
- Phenprobamate
- Procymate
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Nonbenzodiazepines
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- Abecarnil
- Adipiplon
- Alpidem
- CGS-8216
- CGS-9896
- CGS-13767
- CGS-20625
- Divaplon
- ELB-139
- Fasiplon
- GBLD-345
- Gedocarnil
- L-838,417
- NS-2664
- NS-2710
- Ocinaplon
- Pagoclone
- Panadiplon
- Pipequaline
- RWJ-51204
- SB-205,384
- SL-651,498
- Taniplon
- TP-003
- TP-13
- TPA-023
- Y-23684
- ZK-93423
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Pyrazolopyridines
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- Cartazolate
- Etazolate
- ICI-190,622
- Tracazolate
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| α2δ VDCC Blockers |
- Atagabalin
- Gabapentin
- Imagabalin
- PD-217,014
- Pregabalin
- 4-methylpregabalin
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| 5-HT1A Agonists |
- Azapirones: Buspirone
- Gepirone
- Tandospirone; Others: Flesinoxan
- Naluzotan
- Oxaflozane
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| H1 Antagonists |
- Diphenylmethanes: Captodiame
- Hydroxyzine; Others: Brompheniramine
- Chlorphenamine
- Pheniramine
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| CRH1 Antagonists |
- Antalarmin
- CP-154,526
- Pexacerfont
- Pivagabine
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| NK2 Antagonists |
- GR-159,897
- Saredutant
- Ibodutant
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| MCH1 antagonists |
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| mGluR2/3 Agonists |
- Biphenylindanone A
- DCG-IV
- Eglumegad
- HYDIA
- LY-379,268
- LY-404,039
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| mGluR5 NAMs |
- Fenobam
- GRN-529
- MPEP
- MTEP
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| TSPO agonists |
- DAA-1097
- DAA-1106
- Emapunil
- FGIN-127
- FGIN-143
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| σ1 agonists |
- Afobazole
- BD1031
- BD1052
- L-687,384
- Opipramol
- Pentoxyverine
- PRE-084
- SA-4503
- 4-PPBP
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| Others |
- Benzoctamine
- Carbetocin
- Demoxytocin
- Emoxypine
- Mephenoxalone
- Mepiprazole
- Oxanamide
- Oxytocin
- Promoxolane
- Tofisopam
- Trimetozine
- WAY-267,464
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
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proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
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Antidepressants (N06A)
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Specific reuptake inhibitors (RIs), enhancers (REs), and releasing agents (RAs)
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Selective serotonin reuptake inhibitors (SSRIs)
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- Alaproclate
- Citalopram
- Escitalopram
- Femoxetine
- Fluoxetine#
- Fluvoxamine
- Indalpine
- Ifoxetine
- Litoxetine
- Omiloxetine
- Panuramine
- Paroxetine
- Pirandamine
- Seproxetine
- Sertraline
- Zimelidine‡
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Serotonin–norepinephrine reuptake inhibitors (SNRIs)
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- Clovoxamine
- Desvenlafaxine
- Duloxetine
- Levomilnacipran
- Eclanamine
- Milnacipran
- Sibutramine
- Venlafaxine
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Serotonin–norepinephrine–dopamine reuptake inhibitors (SNDRIs)
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- Amitifadine
- Bicifadine
- Brasofensine
- BTS-74,398
- Cocaine
- Diclofensine
- DOV-102,677
- DOV-216,303
- EXP-561
- Fezolamine
- JNJ-7925476
- NS-2359
- PRC200-SS
- Pridefine
- SEP-225,289
- SEP-227,162
- Tesofensine
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Norepinephrine reuptake inhibitors (NRIs)
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- Amedalin
- Atomoxetine/Tomoxetine
- Binedaline
- Ciclazindol
- Daledalin
- Edivoxetine
- Esreboxetine
- Lortalamine
- Maprotiline
- Mazindol
- Nisoxetine
- Reboxetine
- Talopram
- Talsupram
- Tandamine
- Viloxazine
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Dopamine reuptake inhibitors (DRIs)
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Norepinephrine-dopamine reuptake inhibitors (NDRIs)
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- Amineptine
- Bupropion/Amfebutamone
- Cilobamine
- Manifaxine
- Methylphenidate
- Nomifensine
- Radafaxine
- Tametraline
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Norepinephrine-dopamine releasing agents (NDRAs)
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- Amphetamine
- Befuraline
- Lisdexamfetamine
- Methamphetamine
- Phenethylamine
- Piberaline
- Tranylcypromine
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Serotonin-norepinephrine-dopamine releasing agents (SNDRAs)
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- 4-Methyl-αMT
- αET/Etryptamine
- αMT/Metryptamine
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Selective serotonin reuptake enhancers (SSREs)
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Others
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- Indeloxazine
- Teniloxazine
- Tramadol
- Viqualine
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Receptor antagonists and/or reuptake inhibitors
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Serotonin antagonists and reuptake inhibitors (SARIs)
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- Etoperidone
- Lubazodone
- Nefazodone
- Mepiprazole
- Trazodone
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Noradrenergic and specific serotonergic antidepressants (NaSSAs)
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- Aptazapine
- Esmirtazapine
- Mianserin
- Mirtazapine
- Setiptiline/Teciptiline
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Norepinephrine-dopamine disinhibitors (NDDIs)
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Serotonin modulators and stimulators (SMSs)
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Others
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Heterocyclic antidepressants (bi-, tri-, and tetracyclics)
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Bicyclics
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Tricyclics
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- Amezepine
- Amineptine
- Amitriptyline#
- Amitriptylinoxide
- Azepindole
- Butriptyline
- Cianopramine
- Clomipramine
- Cotriptyline
- Cyanodothiepin
- Demexiptiline
- Depramine/Balipramine
- Desipramine
- Dibenzepin
- Dimetacrine
- Dosulepin/Dothiepin
- Doxepin
- Enprazepine
- Fluotracen
- Hepzidine
- Homopipramol
- Imipramine
- Imipraminoxide
- Intriptyline
- Iprindole
- Ketipramine
- Litracen
- Lofepramine
- Losindole
- Mariptiline
- Melitracen
- Metapramine
- Mezepine
- Naranol
- Nitroxazepine
- Nortriptyline
- Noxiptiline
- Octriptyline
- Opipramol
- Pipofezine
- Propizepine
- Protriptyline
- Quinupramine
- Tampramine
- Tianeptine
- Tienopramine
- Trimipramine
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Tetracyclics
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- Amoxapine
- Aptazapine
- Azipramine
- Ciclazindol
- Ciclopramine
- Esmirtazapine
- Maprotiline
- Mazindol
- Mianserin
- Mirtazapine
- Oxaprotiline
- Setiptiline/Teciptiline
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Monoamine oxidase inhibitors (MAOIs)
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Nonselective
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- Irreversible: Benmoxin
- Carbenzide
- Cimemoxin
- Domoxin
- Echinopsidine
- Iproclozide
- Iproniazid
- Isocarboxazid
- Mebanazine
- Metfendrazine
- Nialamide
- Octamoxin
- Phenelzine
- Pheniprazine
- Phenoxypropazine
- Pivalylbenzhydrazine
- Safrazine
- Tranylcypromine
- Reversible: Caroxazone
- Paraxazone
- Quercetin
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MAOA-Selective
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- Reversible: Amiflamine
- Bazinaprine
- Befloxatone
- Berberine
- Brofaromine
- Cimoxatone
- Esuprone
- Eprobemide
- Harmala Alkaloids (Harmine
- Harmaline
- Tetrahydroharmine
- Harman
- Norharman, etc)
- Methylene Blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Sercloremine
- Tetrindole
- Toloxatone
- Tyrima
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MAOB-Selective
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- Irreversible: Ladostigil
- Mofegiline
- Pargyline
- Rasagiline
- Selegiline
- Reversible: Lazabemide
- Milacemide
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Azapirones and other 5-HT1A receptor agonists
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- Alnespirone
- Aripiprazole
- Befiradol
- Buspirone
- Eptapirone
- Flesinoxan
- Flibanserin
- Gepirone
- Ipsapirone
- Oxaflozane
- Tandospirone
- Vilazodone
- Zalospirone
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
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proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
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