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Antipsicóticos de Primeira Geração

Antipsicóticos de Primeira Geração

Os antipsicóticos, também conhecidos como neurolépticos, são utilizados no tratamento de perturbações psicóticas e para alívio da agitação, mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder e agressividade. As suas utilizações mais MAIS Androgen Insensitivity Syndrome notáveis são no tratamento da esquizofrenia e da perturbação bipolar Bipolar Nervous System: Histology e dividem-se em antipsicóticos de 1ª geração ( FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics, pela sigla em inglês) e antipsicóticos atípicos ou de 2ª geração. Os fármacos de ambas as classes atuam nos recetores de dopamina. Alguns dos efeitos adversos mais MAIS Androgen Insensitivity Syndrome relevantes destes agentes incluem distúrbios do movimento, sedação relacionada com a dose e síndrome metabólica. Um efeito colateral mais MAIS Androgen Insensitivity Syndrome sério a longo prazo ao qual se deve ter atenção é a discinesia tardia, que é caraterizada por movimentos involuntários repetitivos.

Last updated: Dec 15, 2025

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Estrutura Química e Farmacodinâmica

Os neurotransmissores que podem ser modulados pelos antipsicóticos de forma a ser obtido um efeito terapêutico incluem a dopamina, a serotonina (também chamada de 5-hidroxitriptamina ( 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS)) e a noradrenalina (NA).

Mecanismo de ação

  • Bloqueio dos recetores de dopamina D2 pós-sinápticos na via mesolímbica → alívio dos sintomas psicóticos
  • Bloqueio das vias mesocortical, nigroestriada e tuberoinfundibular → efeitos adversos
  • Agentes com baixa potência têm maior afinidade por:
    • Recetores alfa-adrenérgicos
    • Recetores histaminérgicos
    • Recetores muscarínicos

Efeitos fisiológicos

  • Recetores dopaminérgicos:
    • Os subtipos D1 e D2 são os alvos farmacológicos.
    • Os recetores do tipo D1 são excitatórios.
    • Os recetores do tipo D2 são inibitórios.
    • Os recetores D2 são expressos em neurónios dopaminérgicos como recetores pré e pós-sinápticos.
  • Hipótese dopaminérgica da esquizofrenia:
    • Hiperfunção da dopamina no estriado (trato mesolímbico) → “sintomas positivos”; Os antipsicóticos de 1ª geração ( FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics, pela sigla em inglês) reduzem:
      • Delírios
      • Alucinações
      • Paranoia
      • Mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder
      • Agressividade
    • Hipofunção da dopamina no córtex pré-frontal (trato mesocortical) → sintomas negativos e cognitivos:
      • Afeto embotido, anedonia, avolia, isolamento social
      • Défice de atenção, memória de trabalho e função executiva
    • Altas doses de psicoestimulantes podem causar psicose.
  • Efeitos do aumento da dopamina nos 2 outros tratos dopaminérgicos cerebrais:
    • No trato nigroestriado: melhoria da função extrapiramidal, por exemplo, os sintomas da doença de Parkinson
    • Na zona quimiorrecetora (centro de vómitocerebral): anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa, náuseas/vómitos
  • Recetores serotoninérgicos ( 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS) :
    • Os principais neurónios produtores de serotonina localizam-se nos núcleos da rafe do tronco cerebral.
    • A 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS é sintetizada nos terminais nervosos serotoninérgicos:
      • Após a propagação de um potencial de ação no neurónio → ocorre fusão das vesículas de armazenamento com a membrana pré-sináptica → libertação de neurotransmissores na fenda sináptica
      • O transportador de serotonina termina a sua atividade → recaptação da 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS no terminal nervoso serotoninérgico
      • A 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS pode ser rearmazenada em vesículas ou metabolizada na membrana mitocondrial externa dos terminais nervosos.
  • Hipótese serotoninérgica da esquizofrenia: Hiperativação dos recetores 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS2A corticais nos neurónios piramidais glutamatérgicos → ↑ libertação de glutamato na área ventral tegmental (VTA, pela sigla em inglês) → sobreativação da via mesolímbica → ↑ libertação de dopamina no estriado

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Farmacocinética e Classificação

Farmacocinética

Existem inúmeros medicamentos cuja farmacocinética é única.

  • Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics atuam no receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors D2.
  • Bem absorvidos:
    • Atravessam facilmente a barreira hematoencefálica
    • Têm semi-vidas longas:
      • A semi-vida dos fármacos administrados por via oral varia desde 30 horas (clorpromazina) até 55 horas (pimozida).
      • Alguns FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics possuem uma via de administração IM (por exemplo, a semi-vida do decanoato de haloperidol Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics IM é de 3 semanas; administrado mensalmente)
    • Os inibidores da citocromo P450 (CYP, pela sigla em inglês) prolongam a ação dos FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics:
      • Os diferentes FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics utilizam uma ou todas as vias CYP2D6, 3A4 e 1A2.
      • A administração de outros medicamentos que sejam substrato destas vias podem provocar sintomas de overdose.
  • Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics necessitam de 1 a 2 semanas até o efeito ser total.
  • Todos os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics, exceto o haloperidol Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics, bloqueiam o recetor de histamina H1.
  • Correspondem a compostos altamente lipossolúveis, alguns dos quais podem ser utilizados na formulação de injetável de ação prolongada (a cada 2-4 semanas)
  • Eliminação: excretados na urina e nas fezes

Classificação

Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics podem ser classificados com base na sua potência:

  • FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics de elevada potência:
    • Baixa atividade nos recetores histamínicos e muscarínicos
    • Mínima associação com os seguintes efeitos adversos:
      • Sedação
      • Aumento de peso
      • Atividade anticolinérgica
    • Alto risco de efeitos colaterais extrapiramidais (EPS, pela sigla em inglês) com todos os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics de elevada potência:
      • Distonia
      • Bradicinésia
      • Acatisia
    • Exemplos:
      • Flufenazina (Prolixina)
      • Haloperidol Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics (Haldol)
      • Loxapina (Loxitane)
      • Perfenazina (genérico)
      • Pimozida (Orap)
      • Tiotixeno (Navane)
      • Trifluoperazina (Stelazina)
  • FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics de baixa potência:
    • Menor afinidade pelos recetores de dopamina; por isso, são necessárias doses mais MAIS Androgen Insensitivity Syndrome elevadas
    • Maior incidência de efeitos colaterais anticolinérgicos e anti-histamínicos
    • Menor incidência de EPS e da síndrome maligna dos neurolépticos ( NMS NMS Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome, pela sigla em inglês)
    • Exemplos:
      • Clorpromazina (Thorazine)
      • Tioridazina (anteriormente conhecido como Mellaril, o produto desta marca foi retirado do mercado mundialmente em 2005 porque causava arritmias cardíacas graves. No entanto, ainda estão disponíveis nos EUA versões genéricas.)

Indicações

  • Patologias tratadas com antipsicóticos de elevada potência:
    • Esquizofrenia:
      • Reduzem os sintomas “positivos” (por exemplo, delírios, agressividade)
      • Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics têm pouco efeito sobre os sintomas “negativos” (por exemplo, anedonia, isolamento social).
      • Antipsicóticos de 2ª geração: mais MAIS Androgen Insensitivity Syndrome eficazes na redução das alterações neurocognitivas
    • Psicose
    • Mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder no contexto de uma perturbação bipolar Bipolar Nervous System: Histology:
      • Utilizados em conjunto com estabilizadores do humor Humor Defense Mechanisms (por exemplo, lítio, ácido valproico e lamotrigina)
      • Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics atuam rapidamente → efeito antimaníaco (os estabilizadores do humor Humor Defense Mechanisms apresentam um período de latência até que os seus efeitos sejam notórios)
    • Perturbação associada a tiques (síndrome de Tourette)
    • Depressão resistente ao tratamento: tratamento adjuvante em combinação com um antidepressivo
    • Demência:
      • Utilizar com cautela em indivíduos com demência grave
      • Utilizados em indivíduos com agressividade ou que representam um perigo para si mesmos ou para os outros
  • Antipsicóticos de baixa potência: clorpromazina (Thorazine)
    • Indicados nas patologias listadas acima
      • Utilizados para o alívio de soluços prolongados
      • Utilizados no tratamento de problemas comportamentais graves em crianças
    • Reduzem o comportamento agressivo, alucinações, pensamentos suicidas/homicidas

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Efeitos Adversos

Os efeitos adversos dos FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics devem-se ao bloqueio da dopamina.

  • Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics de baixa potência (clorpromazina e tioridazina) podem causar:
    • Sedação
    • Hipotensão
    • Efeitos adversos anticolinérgicos:
      • Xerostomia Xerostomia Decreased salivary flow. Sjögren Syndrome
      • Tonturas
      • Visão turva
      • Taquicardia
      • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium
      • Alucinações
  • Os FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics de elevada potência apresentam alto risco de EPS:
    • Distonia aguda: espasmos musculares tónicos prolongados que se desenvolvem rapidamente após o início da medicação (1ºs 4 dias) ou o aumento da dose do antipsicótico
    • Bradicinesia (sintoma parkinsoniano)
    • Acatisia (sensação de inquietação)
    • Perfenazina (genérico): associa-se a menos sintomas extrapiramidais que o FGA haloperidol Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics de elevada potência; comparável à risperidona
  • Aumento do peso
  • Elevação das enzimas hepáticas
  • Problemas oftalmológicos:
    • Retinite pigmentosa (rara)
    • Agravamento do glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
  • Sintomas “Anti-HAM”:
    • H: Sintomas anti-Histamínicos:
    • A: Sintomas anti-Alfa-adrenérgicos:
      • Hipotensão ortostática
      • Arritmias
      • Disfunção sexual
    • M: Sintomas anti-Muscarínicos:
  • Discinesia tardia:
    • Causada por hipersensibilidade do recetor de dopamina pós-sináptico
    • Pode demorar anos ou décadas a aparecer
    • Geralmente, é permanente e angustiante para os indivíduos afetados
    • Manifestações:
      • Movimentos anormais, involuntários e hipercinéticos
      • Tipicamente afeta a boca e a língua, mas também pode afetar o tronco
      • Desfiguração irreversível da face
  • Síndrome maligna dos neurolépticos:
    • Reação aos FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics ameaçadora de vida
    • Provoca hipertermia (febre muito alta)
    • Outros sintomas:
      • Confusão
      • Rigidez muscular
      • Diaforese
      • Taquicardia
  • Hiperprolactinemia (e galactorreia em mulheres e homens)

Interações Medicamentosas e Contra-indicações

Interações farmacológicas

  • Os antiácidos ↓ a absorção de flufenazina e trifluoperazina
  • Deve ser evitada a utilização de FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics juntamente com qualquer agente prolongador do QT.
  • Os indutores da CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) interagem com a pimozida:
    • Carbamazepina
    • Interação medicamento-alimento com o sumo de toranja
  • Os inibidores da CYP1A2 interagem com o tiotixeno e a trifluoperazina.
  • Os inibidores da CYP2D6 interagem com a perfenazina e a clorpromazina:
    • Fluoxetina
    • Paroxetina
    • Bupropiom

Contraindicações

  • Lista de Beers: lista de medicamentos potencialmente inadequados em idosos
    • Foi originalmente publicada em 1991 e é atualizada regularmente
    • Todos os antipsicóticos estão listados na lista de Beers.
  • Alerta geral “Black-box” da FDA: Todos os antipsicóticos aumentam o risco de morte em idosos com psicose relacionada com a demência.
  • SNC:
    • Indivíduos em coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma ou com depressão do SNC
    • Utilização concomitante de hipnóticos em alta dose
    • Doença de Parkinson
  • Cardiovasculares:
    • Arritmias
    • Síndrome do QT longo congénito
  • Hematológicas:
    • Discrasias sanguíneas
    • Medula óssea suprimida

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Referências

  1. Mann, S. K., & Marwaha, R. (2023). Chlorpromazine. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK553079/
  2. Meyer, J.M. (2018). Pharmacotherapy of Psychosis and Mania. In Brunton, L.L., Hilal-Dandan, R., Knollmann, B.C. (Eds.) Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13e. New York, NY: McGraw-Hill. 
  3. Nelson, L.S., et al. (2019). Neurotransmitters and Neuromodulators. In Goldfrank’s Toxicologic Emergencies, 11e. New York, NY: McGraw-Hill.
  4. Schatzberg, A.F., DeBattista, C. (2019). Schatzberg’s Manual of Clinical Psychopharmacology, 9e. Washington, DC: American Psychiatric Association Publishing.
  5. Kaar, S.J., et al. (2020). Antipsychotics: Mechanisms underlying clinical response and side effects and novel treatment approaches based on pathophysiology. Neuropharmacology. 172, 107704. https://doi.org/10.1016/j.neuropharm.2019.107704 
  6. Mandrioli, R., et al. (2015). Evaluation of the pharmacokinetics, safety, and clinical efficacy of ziprasidone for the treatment of schizophrenia and bipolar disorder. Expert Opinion on Drug Metabolism and Toxicology. 11, 149–174. https://doi.org/10.1517/17425255.2015.991713 
  7. Citrome, L. (2015). The ABCs of dopamine receptor partial agonists — aripiprazole, brexpiprazole, and cariprazine: the 15-min challenge to sort these agents out. The International Journal of Clinical Practice. 69, 1211–1220. https://doi.org/10.1111/ijcp.12752 
  8. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Arlington, VA, American Psychiatric Association.
  9. American Geriatrics Society. (2019). 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatric Society. 67, 674–694. https://doi.org/10.1111/jgs.15767 
  10. Jibson, M.D. (2025). First-generation antipsychotic medications: Pharmacology, administration, and comparative side effects. UpToDate. Retrieved November 19, 2025, from https://www.uptodate.com/contents/first-generation-antipsychotic-medications-pharmacology-administration-and-comparative-side-effects
  11. Lexicomp, Inc. (2021). Pimozide: Drug information. UpToDate. Retrieved November 19, 2025, from https://www.uptodate.com/contents/pimozide-drug-information
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