Abstract
Antidepressants, antiepileptics, mood stabilizers, and antipsychotics are extremely broadly used psychoactive drugs. These drug terms are universally used in the literature. However, the indications of these drugs have broadened substantially and overlap. The mismatch between drug classification and clinical uses causes a lot of confusion in communication and renders literature searches increasingly difficult. Therefore, we propose to drop the above terms altogether and replace them by simple mechanistic terms. Antidepressants are re-named as norepinephrine/serotonin (NE/5-HT) enhancers, antiepileptics comprising drugs with different mechanisms become neuronal inhibitors with pleiotropic effects (NIPEs), and antipsychotics become antagonists at multiple G protein–coupled receptors (mGPCR antagonists). Alkali metal ions, comprising lithium, are integrated into NIPEs. The terms “typical/first-generation/conventional” and “atypical/second-generation/non-conventional” antipsychotics should be dropped, because the original criterion for distinction, i.e., the presence and absence of extrapyramidal motor effects, respectively, is not valid anymore. The suggested changes in drug nomenclature have already been implemented into a recent textbook (Seifert R, Basic Knowledge of Pharmacology). The revised nomenclature ensures consistency with other fields of pharmacology and assignment of drug classes to indications without causing confusion. The authors acknowledge that the change in drug nomenclature is a cultural process that will take time and openly discuss the problems associated with the proposal. Ultimately, international learned societies will have to agree on a new nomenclature.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
The status quo of psychoactive drug terminology
Psychoactive drugs are extremely broadly prescribed both by psychiatrists and general practitioners. Traditionally, psychotropic drugs are divided into antidepressants, antiepileptics (or anticonvulsants), mood stabilizers, and antipsychotics (originally designated as neuroleptics). These terms are based on the traditional indications for these drugs. In the literature, the terms are broadly used: Fig. 1 shows the frequency of use of these terms in the medical literature based on a recent PubMed search. Both absolute numbers and relative numbers of the use of terms are reported. The legend of Fig. 1 describes the general search strategy and Supplementary Table 1 describes the specific search terms used. Supplementary Table 2 shows the source data for the graphs shown in Fig. 1. For the sake of focus of this article, we analyzed only selected classes of psychoactive drugs and did not consider, e.g., barbiturates, benzodiazepines, μ-opioid receptor agonists, and acetylcholine esterase inhibitors.
Originally, antidepressants had been exclusively used for depression, antiepileptics for epilepsy, mood stabilizers for bipolar disorder, and antipsychotics for schizophrenia and acute mania. However, this traditional classification started to erode already many years ago when it became clear that the mood stabilizer lithium can be used as augmentation therapy for depression and that antiepileptics can be effectively used for mood stabilization in bipolar disorder (Kaufman 2011; Nelson et al. 2014; Baldessarini et al. 2019). Paradoxically, while indications had started to expand a long time ago, drug nomenclature remained the same, largely due to language used in pharmacology textbooks.
For antipsychotics, the situation is even more complicated. Major adverse reactions of antipsychotics such as haloperidol, particularly in high doses prescribed previously, are extrapyramidal motor symptoms (EPSs). These EPSs, specifically Parkinsonian symptoms, akathisia and tardive dyskinesia, can limit therapy with these drugs (Casey 2006; Divac et al. 2014; Sykes et al. 2017; Hirano 2018). The serious EPSs of the original antipsychotics constituted the motivation to develop antipsychotics with fewer or even no EPSs. Because EPSs are so serious, clinicians and scientists alike aimed at classifying drugs into antipsychotics with EPS risk and antipsychotics without EPS risk.
Therefore, the terms first-generation and second-generation antipsychotics were coined. Figure 2 shows the absolute and relative frequency of use of these terms in the medical literature based on a PubMed search. The legend of Fig. 2 describes the general search strategy and Supplementary Table 1 describes the specific search terms used. Supplementary Table 3 shows the source data for the graphs shown in Fig. 2. Alternatively to first-generation and second-generation antipsychotics, the terms typical and atypical antipsychotics were introduced. As a third option, the term conventional antipsychotics was introduced, but the term non-conventional or unconventional antipsychotics is not used in the literature. The situation is further complicated by the fact that, instead of the term antipsychotics, the term neuroleptics is used, although now much less commonly than in the past. As a result, we have at least three different terms with the same meaning for a given class of psychoactive drugs, and the terms are arbitrarily used in the literature.
Use of terms for psychoactive drugs in the literature
Anticonvulsants and antiepileptics designate one and the same drug class originally developed to treat epilepsies. The term anticonvulsant was initially used more often in absolute numbers than the term antiepileptic, but these days, the term antiepileptic is used more often (Fig. 1a, b). With respect to relation to the disease epilepsy, the term antiepileptics is more appropriate.
The use of the term mood stabilizer has strongly increased since the 1990s and plateaued in recent years (Fig. 1c). The term antidepressant has increased linearly in terms of absolute publications and almost exponentially in terms of relative publications for many years with a plateau during the preceding years (Fig. 1d). The term antipsychotics has increased exponentially in absolute and relative terms for many years and has plateaued recently (Fig. 1e). Until the year 2000, the term antipsychotic competed strongly with the term neuroleptic in the literature (Fig. 1f). However, since the term antipsychotic describes the clinical use of the drugs more precisely (treatment of psychoses) than the term neuroleptic, use of the latter term has declined since the mid-1990s.
The term typical antipsychotics (Fig. 2c) appeared before the term conventional antipsychotics and then followed by first-generation antipsychotics (Fig. 2a, e). The three terms describe the same group of drugs. During recent years, use of the term conventional antipsychotics has declined as has, to a lesser extent, the term typical antipsychotic. Interestingly, the terms non-conventional or unconventional antipsychotics are not used in the literature. The term atypical antipsychotics is still used more commonly than the term second-generation antipsychotics (Fig. 2b, d).
Problems associated with inconsistent drug nomenclature
There are numerous problems associated with inconsistent drug nomenclature. First of all, the literature search becomes exceedingly difficult and prone to errors and omissions due to the existence of multiple terms for one and the same group of drugs. Not every clinician or researcher may be aware of these duplications or it may be wrongly assumed that different terms have actually a different meaning.
Most importantly, the clinical use of drugs has expanded dramatically over the years. For example, antidepressants are often used for obsessive-compulsive disorder, anxiety disorder, and post-traumatic stress disorder (Skapinakis et al. 2016; Locher et al. 2017; Vries et al. 2018; Amerio et al. 2019; Slee et al. 2019; Stone 2019). Antiepileptics are used for many other diseases than epilepsy including prevention of migraine and trigeminal neuralgia, polyneuropathies, restless leg syndrome, fibromyalgia, and bipolar disorder (Zilliox and Russell 2011; Kaufman 2011; Qin et al. 2018; Hirakata et al. 2018; Salminen and Winkelmann 2018; Parikh and Silberstein 2019), just to mention some indications. Similarly, antipsychotics are used for many more diseases than schizophrenia and acute mania including depression, borderline personality disorders, anxiety disorder, Tourette syndrome, and autism (Ceskova and Silhan 2018; Carulla-Roig et al. 2018; Slee et al. 2019; Baldessarini et al. 2019; Stone 2019; Fallah et al. 2019). The mood stabilizer lithium is used not only for bipolar disorder but also for augmentation in severe depression (Kleeblatt et al. 2017; Baldessarini et al. 2019). Moreover, the use of lithium in neurodegenerative diseases is being explored (Huraskin and Horn 2019; Hampel et al. 2019). These data clearly document an increasing mismatch between drug terminology and clinical drug use. This is also a substantial problem in practical drug prescription and administration. For example, it takes lengthy explanation, why a patient should take an antipsychotic for an anxiety disorder although the patient does not suffer from psychosis. This mismatch may have negative consequences for drug adherence. In addition, the patient may assume that she/he is already so ill that she/he suffers from psychosis and consequently feels worse.
The issue of mismatch between terminology and clinical effects is particularly striking for the atypical and atypical antipsychotics (and synonymous terms). Clinical studies have clearly revealed that the original claim to distinguish between the drug classes, i.e., the presence and absence, respectively, of EPSs, is not valid. Rather, commonly used atypical antipsychotic drugs such as risperidone, olanzapine, and quetiapine possess a significant risk for EPSs (Fischer-Barnicol et al. 2008; Sykes et al. 2017). The only difference between these drugs and haloperidol is that reports on EPSs for haloperidol appeared earlier in the literature (Fig. 2f). This difference is just the result of the fact that risperidone, olanzapine, and quetiapine were introduced later than haloperidol.
Proposed solution to the problem—Step 1: Get rid of traditional terms
The nomenclature issue has been recognized for some time, and within the discipline of neuropharmacology, a solution has been attempted by developing a multidimensional classification of psychoactive drugs (Zohar et al. 2014, 2015; Rao and Andrade 2016; Caraci et al. 2017). However, it turned out that the nomenclature is too complex, specifically for use in the clinic. Another important issue is that neuropsychopharmacology constitutes only one subfield of pharmacology, and any given nomenclature should be consistent with the nomenclature used in other subfields of pharmacology.
In a recent review, one of the authors of this article proposed to implement, throughout the entire field of pharmacology, a mechanism-based nomenclature of drugs that refrains from using specific indications (Seifert 2018). In fact, the mechanism of action of a drug does not change, but the clinical uses do. In the previous review, the field of neuropsychopharmacology was intentionally not covered because, at that time, a practical solution had not yet been developed.
In the meantime, the process has advanced, and a simple and practical solution can be presented. The proposed nomenclature is simple, uses just few terms, focuses on mechanisms of action, is neutral with respect to clinical uses, and is consistent with nomenclature in other fields of pharmacology.
Table 1 lists the problematic terms, their suggested replacements, and the rationale. The term antidepressants should be replaced by norepinephrine/serotonin (NE/5-HT) enhancers, describing the overarching mechanism of action of these drugs (Di Giovanni et al. 2016; Marazziti 2017; Cheffer et al. 2018). Additionally, the term NE/5-HT enhancer has a more positive connotation than antidepressant and avoids use of the term depression which has a strong negative bias. It will be much easier for a physician to prescribe a NE/5-HT enhancer than an antidepressant for obsessive-compulsive disorder or anxiety disorder.
The antiepileptics (anticonvulsants) comprise many heterogeneous groups of drugs with different mechanisms of action including sodium and calcium channel blockade and inhibition of glutamatergic mechanisms (Kobayashi et al. 2019). Thus, as a new umbrella term, we propose to use the term neuronal inhibitors with pleiotropic effects because the overall mechanism of action of these drugs is to reduce neuronal excitability. The term pleiotropic alludes to the fact that neuronal inhibition can be exploited in numerous indications.
The term mood stabilizer should also be abandoned because it is not clearly defined. Certain antiepileptics have mood-stabilizing properties as has the alkali ion lithium. Therefore, lithium could be placed into the group of NIPEs.
The term antipsychotics should be replaced by antagonists at multiple GPCRs (mGPCR antagonists) because this is the molecular mechanism underlying all antipsychotics (Gray and Roth 2007; Kahn et al. 2015; Kondej et al. 2018). The term mGPCR antagonists is neutral with respect to clinical use and readily allows for expansion of clinical uses. As another advantage, the efficacy of mGPCR antagonists in so many different psychiatric diseases indicates that, although phenotypically quite different, they may have a common pathophysiological basis. As pointed out above, the terms first generation/typical/conventional antipsychotics/neuroleptics as well as second-generation/atypical and unconventional antipsychotics are arbitrary and, hence, dispensable.
Proposed solution to the problem—Step 2: Set up a mechanism-based nomenclature
In the preceding section, a number of broad new mechanism-based terms for psychotropic drugs were proposed. These terms describe systems that can be further divided into various drug classes which are represented by various drugs possessing various indications. Table 2 presents this system with 4 hierarchy levels (system ➔ drug class ➔ individual drug ➔ indication). The advantage of the system is that indications are at the lowest hierarchy level and can be readily adjusted for any given drug without affecting higher hierarchy level terms.
The system of NE/5-NT enhancers is divided into the drug classes of α2AR antagonists, NSMRIs, SSRIs, SSNRIs, and MAO inhibitors. Additional drug classes can be readily added. Each drug class is then populated with various drugs to which specific indications are assigned.
The system of NIPEs is divided into various drug classes according to mechanism of action. Lithium is integrated into this system as well. However, since the mechanism of action of lithium is not yet known, a mechanistic class assignment is problematic. Rather, a chemistry-based term (alkali ion) is used. This neutral term could be replaced by a mechanism-based term at a later stage.
With respect to the mGPCR antagonists, one can define two broad classes of drugs. On one hand, we have drugs, haloperidol being the prototype, with affinity to multiple GPCRs and a high affinity to the D2R. These drugs can be designated as D2R-mGPCR antagonists. These drugs are characterized by a high risk of EPSs (Sykes et al. 2017). Many mGPCR antagonists are characterized by drug-specific pharmacological profiles, and it is rather difficult to assign a specific affinity for a given receptor to a given neuropsychiatric clinical effect. In addition, these drugs may or may not have the potential for EPSs. For example, clozapine has a low EPS risk, but other drugs such as risperidone have a higher EPS risk (Azorin et al. 2001). Moreover, the clinical uses of the drugs vary broadly (see Table 2). Accordingly, all drugs that are not characterized by a high D2R affinity relative to other GPCRs could be classified as pleiotropic mGPCR antagonists (p-mGPCR antagonists), alluding to the fact that these drugs have pleiotropic receptor profiles, pleiotropic therapeutic effects, and pleiotropic adverse reactions. This classification avoids making the incorrect distinction between drugs with high EPS risk and no EPS risk.
A major mechanistic implication of the change from antipsychotics to mGPCR antagonists is the fact that, in the new terminology, the words “GPCR” and “antagonist” are present. This is clinically relevant for three reasons. First, drugs acting via GPCRs show rapid clinical effects as compared with NE/5-HT enhancers. Second, GPCR antagonists, unlike GPCR agonists, do not exhibit desensitization and loss of efficacy during long-term therapy. Accordingly, in general, the drug dose does not have to be increased during long-term therapy. Third, GPCR antagonists do NOT cause addiction. This is a very important piece of information for patients who often fear that all psychoactive drugs cause addiction and tolerance. Last but not least, the terminology is consistent with other pharmacological fields; i.e., we have the terms H1R antagonists, β1AR antagonists, and MxR antagonists, to name few examples. The fact that in case of antipsychotics not a single GPCR is mentioned but rather GPCRs in general reflects the fact that these drugs bind to multiple receptors and have diverse therapeutic and adverse effects. Thus, the new nomenclature will, after some adjustment, render drug therapy and literature searches easier and logical and increase patient adherence.
Where do we stand now?
It is beginning to emerge that, in many fields of medicine, a system- and mechanism-based approach is much more useful than the traditional organ- and disease-specific approach (Saltiel et al. 2015; Ramos and Bentires-Alj 2015; Gebicke-Haerter 2016; Walter et al. 2016; Bennett 2017; Zhou et al. 2018; Willsey et al. 2018). This strategy can and should be readily expanded to pharmacology as a whole and psychopharmacology in particular. The problem is that several generations of physicians, scientists, and pharmacists have learned the traditional nomenclature and are used to work with the system despite its apparent weaknesses and problems. Thus, it cannot be expected that the present proposal is enthusiastically embraced by all members of the medical and scientific community immediately. It is a process.
In Germany, the medical educational system has recently agreed on a mechanism-based drug nomenclature. This nomenclature has been published by the Institut für Medizinische and Pharmazeutische Prüfungsfragen (IMPP, Institute for Medical and Pharmaceutical Exam Questions) in November 2019 (IMPP-GK2, 5th edition, effective spring 2022): https://www.impp.de/pruefungen/allgemein/gegenstandskataloge.html. To integrate this nomenclature into pharmacology teaching of medical students, one of the authors of this article has written a textbook in English language (Seifert 2019) and German language (Seifert 2020) using the new nomenclature.
General discussion
It must be emphasized that this article reflects the position of the authors but not international learned societies such as the International Union of Pharmacologists (IUPHAR). A logical next step will be to discuss this proposal at the IUPHAR level. The discussion of the topic will also have to involve psychiatrists. A better molecular characterization of psychiatric diseases and improved understanding of their pathophysiology will improve the matching of diseases to appropriate drugs (Kahn et al. 2015; Hirschtritt and Insel 2018; Kim and Park 2019).
It is also acknowledged that the proposed nomenclature does not only solve some problems but also creates problems. For example, one may argue that placing lithium with a still unknown mechanism of action (Won and Kim 2017) into the group of NIPEs leads to a substantial loss in granularity. Along the same line, some mGPCR antagonists (such as diphenhydramine) are predominantly used for the treatment of non-psychiatric diseases (Palmer et al. 2020; Fein et al. 2019), and how many GPCRs does a drug have to antagonize to be classified as mGPCR antagonist? Does, e.g., propranolol fulfill the criteria of a mGPCR antagonist (Cernecka et al. 2014)? Last but not least, how can we integrate pluridimensional efficacy, biased signaling, and allosteric GPCR modulators (Hauser et al. 2017; Seyedabadi et al. 2019; Kenakin 2019) into the classification without rendering it too complicated for the physician? We hope that, with this article, we initiate a discussion at an international level that contributes to improving drug classification of, and communication about, psychotropic drugs and ultimately improves drug safety.
References
Amerio A, Tonna M, Odone A (2019) Clinical management of comorbid bipolar disorder and obsessive-compulsive disorder: a case series. Acta Biomed 89:581–584
Andrisano C, Chiesa A, Serretti A (2013) Newer antidepressants and panic disorder: a meta-analysis. Int Clin Psychopharmacol 28:33–45
Azorin J-M, Spiegel R, Remington G, Vanelle JM, Péré JJ, Giguere M, Bourdeix I (2001) A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia. Am J Psychiatry 158:1305–1313
Bai Z, Wang G, Cai S, Ding X, Liu W, Huang D, Shen W, Zhang J, Chen K, Yang Y, Zhang L, Zhao X, Ouyang Q, Zhao J, Lu H, Hao W (2017) Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: a network meta-analysis. Schizophr Res 185:73–79
Baldessarini RJ, Tondo L, Vázquez GH (2019) Pharmacological treatment of adult bipolar disorder. Mol Psychiatry 24:198–217
Bennett MI (2017) Mechanism-based cancer-pain therapy. Pain 158:S74–S78
Caraci F, Enna SJ, Zohar J, Racagni G, Zalsman G, van den Brink W, Kasper S, Koob GF, Pariante CM, Piazza PV, Yamada K, Spedding M, Drago F (2017) A new nomenclature for classifying psychotropic drugs. Br J Clin Pharmacol 83:1614–1616
Carulla-Roig M, Isomura K, Pérez-Vigil A, Larsson H, Hellner C, Mataix-Cols D, Fernández de la Cruz L (2018) Pharmacoepidemiology of Tourette and chronic tic disorders in Sweden 2005-2013. J Child Adolesc Psychopharmacol 28:637–645
Casey DE (2006) Implications of the CATIE trial on treatment: extrapyramidal symptoms. CNS Spectr 11:25–31
Cernecka H, Sand C, Michel MC (2014) The odd sibling: features of β3-adrenoceptor pharmacology. Mol Pharmacol 86:479–484
Ceskova E, Silhan P (2018) Novel treatment options in depression and psychosis. Neuropsychiatr Dis Treat Volume 14:741–747
Chang K-H, Wang S-H, Chi C-C (2015) Efficacy and safety of topiramate for essential tremor. Medicine (Baltimore) 94:e1809
Cheffer A, Castillo ARG, Corrêa-Velloso J, Gonçalves MCB, Naaldijk Y, Nascimento IC, Burnstock G, Ulrich H (2018) Purinergic system in psychiatric diseases. Mol Psychiatry 23:94–106
Del Casale A, Sorice S, Padovano A, Simmaco M, Ferracuti S, Lamis DA, Rapinesi C, Sani G, Girardi P, Kotzalidis GD, Pompili M (2019) Psychopharmacological treatment of obsessive-compulsive disorder (OCD). Curr Neuropharmacol 17:710–736
Di Giovanni G, Svob Strac D, Sole M et al (2016) Monoaminergic and histaminergic strategies and treatments in brain diseases. Front Neurosci 10:541
Divac N, Prostran M, Jakovcevski I, Cerovac N (2014) Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int 2014:656370
Fallah MS, Shaikh MR, Neupane B, Rusiecki D, Bennett TA, Beyene J (2019) Atypical antipsychotics for irritability in pediatric autism: a systematic review and network meta-analysis. J Child Adolesc Psychopharmacol 29:168–180
Fein MN, Fischer DA, O’Keefe AW, Sussman GL (2019) CSACI position statement: newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for treatment of allergic rhinitis and urticaria. Allergy Asthma Clin Immunol 15:61
Fischer-Barnicol D, Lanquillon S, Haen E, Zofel P, Koch HJ, Dose M, Klein HE, Working Group 'Drugs in Psychiatry' (2008) Typical and atypical antipsychotics--the misleading dichotomy. Results from the Working Group “Drugs in Psychiatry” (AGATE). Neuropsychobiology 57:80–87
Gebicke-Haerter PJ (2016) Systems psychopharmacology: a network approach to developing novel therapies. World J Psychiatry 6:66–83
Graham B, Garcia NM, Burton MS, Cooper AA, Roy-Byrne PP, Mavissakalian MR, Feeny NC, Zoellner LA (2018) High expectancy and early response produce optimal effects in sertraline treatment for post-traumatic stress disorder. Br J Psychiatry 213:704–708
Gray JA, Roth BL (2007) The pipeline and future of drug development in schizophrenia. Mol Psychiatry 12:904–922
Hampel H, Lista S, Mango D et al (2019) Lithium as a treatment for Alzheimer’s disease: the systems pharmacology perspective. J Alzheimers Dis 69:615–629
Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE (2017) Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov 16:829–842
Hirakata M, Yoshida S, Tanaka-Mizuno S et al (2018) Pregabalin prescription for neuropathic pain and fibromyalgia: a descriptive study using administrative database in Japan. Pain Res Manag 2018:2786151
Hirano Y (2018) Risk of extrapyramidal syndromes associated with psychotropic polypharmacy: a study based on large-scale Japanese claims data. Ther Innov Regul Sci 216847901880824. https://doi.org/10.1177/2168479018808248
Hirschtritt ME, Insel TR (2018) Digital technologies in psychiatry: present and future. Focus (Am Psychiatr Publ) 16:251–258
Huraskin D, Horn AHC (2019) Alkali ion influence on structure and stability of fibrillar amyloid-β oligomers. J Mol Model 25:37
Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, O'Donovan M, Correll CU, Kane JM, van Os J, Insel TR (2015) Schizophrenia. Nat Rev Dis Prim 1:15067
Kaufman KR (2011) Antiepileptic drugs in the treatment of psychiatric disorders. Epilepsy Behav 21:1–11
Kenakin TP (2008) Pharmacological onomastics: what’s in a name? Br J Pharmacol 153:432–438
Kenakin T (2019) Emergent concepts of receptor pharmacology. Handb Exp Pharmacol 260:17–41
Kim YK, Park SC (2019) Classification of psychiatric disorders. Adv Exp Med Biol 1192:17–25
Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S (2017) Efficacy of off-label augmentation in unipolar depression: a systematic review of the evidence. Eur Neuropsychopharmacol 27:423–441
Kobayashi K, Endoh F, Ohmori I, Akiyama T (2019) Action of antiepileptic drugs on neurons. Brain Dev 42:2–5. https://doi.org/10.1016/j.braindev.2019.07.006
Kondej M, Stępnicki P, Kaczor AA et al (2018) Multi-target approach for drug discovery against schizophrenia. Int J Mol Sci 19:3105
Kusumi I, Boku S, Takahashi Y (2015) Psychopharmacology of atypical antipsychotic drugs: from the receptor binding profile to neuroprotection and neurogenesis. Psychiatry Clin Neurosci 69:243–258
Locher C, Koechlin H, Zion SR, Werner C, Pine DS, Kirsch I, Kessler RC, Kossowsky J (2017) Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents. JAMA Psychiatry 74:1011–1020
Mallick-Searle T, Snodgrass B, Brant J (2016) Postherpetic neuralgia: epidemiology, pathophysiology, and pain management pharmacology. J Multidiscip Healthc Volume 9:447–454
Marazziti D (2017) Understanding the role of serotonin in psychiatric diseases. F1000Research 6:180
Nelson JC, Baumann P, Delucchi K, Joffe R, Katona C (2014) A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression. J Affect Disord 168:269–275
Palmer RB, Reynolds KM, Banner W, Bond GR, Kauffman RE, Paul IM, Green JL, Dart RC (2020) Adverse events associated with diphenhydramine in children, 2008-2015. Clin Toxicol (Phila) 58:99–106
Parikh SK, Silberstein SD (2019) Current status of antiepileptic drugs as preventive migraine therapy. Curr Treat Options Neurol 21:16
Pringsheim T, Holler-Managan Y, Okun MS, Jankovic J, Piacentini J, Cavanna AE, Martino D, Müller-Vahl K, Woods DW, Robinson M, Jarvie E, Roessner V, Oskoui M (2019) Comprehensive systematic review summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 92:907–915
Qin Z, Xie S, Mao Z, Liu Y, Wu J, Furukawa TA, Kwong JSW, Tian J, Liu Z (2018) Comparative efficacy and acceptability of antiepileptic drugs for classical trigeminal neuralgia: a Bayesian network meta-analysis protocol. BMJ Open 8:e017392
Ramos P, Bentires-Alj M (2015) Mechanism-based cancer therapy: resistance to therapy, therapy for resistance. Oncogene 34:3617–3626
Rao TS, Andrade C (2016) Classification of psychotropic drugs: problems, solutions, and more problems. Indian J Psychiatry 58:111–113
Salminen AV, Winkelmann J (2018) Restless legs syndrome and other movement disorders of sleep-treatment update. Curr Treat Options Neurol 20:55. https://doi.org/10.1007/s11940-018-0540-3
Saltiel PF, Silvershein DI, Silvershein D (2015) Major depressive disorder: mechanism-based prescribing for personalized medicine. Neuropsychiatr Dis Treat 11:875–888
Seifert R (2018) Rethinking pharmacological nomenclature. Trends Pharmacol Sci 39(9):785–797
Seifert R (2019) Basic knowledge of pharmacology. Springer International Publishing, Cham
Seifert R (2020) Basiswissen Pharmakologie, 2nd edn. Springer-Verlag, Berlin/Heidelberg
Seyedabadi M, Ghahremani MH, Albert PR (2019) Biased signaling of G protein coupled receptors (GPCRs): molecular determinants of GPCR/transducer selectivity and therapeutic potential. Pharmacol Ther 200:148–178
Siskind D, McCartney L, Goldschlager R, Kisely S (2016) Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. Br J Psychiatry 209:385–392
Skapinakis P, Caldwell DM, Hollingworth W, Bryden P, Fineberg NA, Salkovskis P, Welton NJ, Baxter H, Kessler D, Churchill R, Lewis G (2016) Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis. The Lancet Psychiatry 3:730–739
Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N (2019) Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet 393:768–777
Stone MH (2019) Borderline personality disorder: clinical guidelines for treatment. Psychodyn Psychiatry 47:5–26
Sykes DA, Moore H, Stott L, Holliday N, Javitch JA, Lane JR, Charlton SJ (2017) Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors. Nat Commun 8:763
Taciak PP, Lysenko N, Mazurek AP (2018) Drugs which influence serotonin transporter and serotonergic receptors: pharmacological and clinical properties in the treatment of depression. Pharmacol Rep 70:37–46
Vermeulen JM, van Rooijen G, van de Kerkhof MPJ, Sutterland AL, Correll CU, de Haan L (2019) Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.1-12.5 years. Schizophr Bull 45:315–329
Vries YA, Roest AM, Burgerhof JGM, Jonge P (2018) Initial severity and antidepressant efficacy for anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder: an individual patient data meta-analysis. Depress Anxiety 35:515–522
Walter JE, Farmer JR, Foldvari Z, Torgerson TR, Cooper MA (2016) Mechanism-based strategies for the management of autoimmunity and immune dysregulation in primary immunodeficiencies. J Allergy Clin Immunol Pract 4:1089–1100
Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ (2018) The psychiatric cell map initiative: a convergent systems biological approach to illuminating key molecular pathways in neuropsychiatric disorders. Cell 174:505–520
Won E, Kim YK (2017) An oldie but goodie: lithium in the treatment of bipolar disorder through neuroprotective and neurotrophic mechanisms. Int J Mol Sci 18:E2679
Zhou X, Lei L, Liu J, Halu A, Zhang Y, Li B, Guo Z, Liu G, Sun C, Loscalzo J, Sharma A, Wang Z (2018) A systems approach to refine disease taxonomy by integrating phenotypic and molecular networks. EBioMedicine 31:79–91
Zilliox L, Russell JW (2011) Treatment of diabetic sensory polyneuropathy. Curr Treat Options Neurol 13:143–159
Zohar J, Nutt DJ, Kupfer DJ, Moller HJ, Yamawaki S, Spedding M, Stahl SM (2014) A proposal for an updated neuropsychopharmacological nomenclature. Eur Neuropsychopharmacol 24:1005–1014
Zohar J, Stahl S, Moller H-J, Blier P, Kupfer D, Yamawaki S, Uchida H, Spedding M, Goodwin GM, Nutt D (2015) A review of the current nomenclature for psychotropic agents and an introduction to the neuroscience-based nomenclature. Eur Neuropsychopharmacol 25:2318–2325
Zulfarina MS, Syarifah-Noratiqah S-B, Nazrun SA, Sharif R, Naina-Mohamed I (2019) Pharmacological therapy in panic disorder: current guidelines and novel drugs discovery for treatment-resistant patient. Clin Psychopharmacol Neurosci 17:145–154
Funding
Open Access funding provided by Projekt DEAL.
Author information
Authors and Affiliations
Contributions
RS and BS jointly developed the concept and jointly wrote the manuscript. RS and BS read and approved the final manuscript.
Corresponding author
Ethics declarations
The authors complied with all ethical standards of scientific conduct.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Seifert, R., Schirmer, B. A simple mechanistic terminology of psychoactive drugs: a proposal. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1331–1339 (2020). https://doi.org/10.1007/s00210-020-01918-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-020-01918-x