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You are watching: Which statement is true regarding antipsychotic drugs?

StatPearls . Treasure Island (FL): StatPearls Publishing; 2021 Jan-.


Continuing education and learning Activity

First-generation antipsychotics room dopamine receptor antagonists (DRA) and are recognized as common antipsychotics. Second-generation antipsychotics room serotonin-dopamine antagonists and also are additionally known together atypical antipsychotics. This task outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, monitoring, and also toxicity of antipsychotic medications.

Review some interprofessional team strategies for improving care coordination and also communication to advance appropriate clinical outcomes through antipsychotic therapy to act indicated conditions leading come optimal patient outcomes.


First-generation antipsychotics are dopamine receptor antagonists (DRA) and also are recognized as common antipsychotics. They include phenothiazines (trifluoperazine, perphenazine, prochlorperazine, acetophenazine, triflupromazine, mesoridazine), butyrophenones (haloperidol), thioxanthenes (thiothixene, chlorprothixene), dibenzoxazepines (loxapine), dihydroindoles (molindone), and diphenylbutylpiperidines (pimozide).<1><2><3>

Second-generation antipsychotics space serotonin-dopamine antagonists and also are likewise known as atypical antipsychotics. The Food and Drug administration (FDA) has approved 12 patent antipsychotics together of the year 2016. They room risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole, and clozapine.<4>


Acute Mania: First-generation antipsychotics are effective in the therapy of acute mania through psychotic symptoms. All second-generation antipsychotics except clozapine can additionally be provided as a therapy of symptom of acute mania. Antipsychotics are supplied with atmosphere stabilizers like lithium, valproic acid, or carbamazepine initially, and also then after symptom stabilize have the right to be slowly decreased and withdrawn.
Major Depressive Disorder through Psychotic features: very first or second-generation antipsychotics, together with an antidepressant, is the treatment of choice for depression through psychotic features. Olanzapine and also fluoxetine, together a combination therapy, have actually FDA approval for treatment-resistant depression.
Delusional Disorder: First-generation antipsychotics are shown in the treatment of delusional disorder and paranoia connected with personality disorders.
Severe Agitation: Severely agitated, irritable, hostile, and also hyperactive patients have the right to be treated with a short-term course the first-generation antipsychotics irrespective of the etiology that the behavior disturbance. Second-generation antipsychotics can also be used for dealing with acute agitation. Antipsychotics can additionally be offered in youngsters with severe autism exhibiting behavior disturbances though repeatedly giving antipsychotics is not preferred. Risperidone and also olanzapine are advantageous for regulating aggression in children.
Tourette Disorder: Haloperidol and pimozide space the antipsychotics most typically used for this syndrome. Tourette disorder is one off-label indication for second-generation antipsychotics.
Borderline Personality Disorder: This form of personality disorder have the right to have symptoms of psychosis and paranoia. Both very first and second-generation antipsychotics are used for the therapy of these symptoms.
Dementia and also Delirium: A short dose that high potential first-generation antipsychotics favor haloperidol is recommended for the treatment of agitation in delirium and also dementia. That is vital to usage caution in yonsi patients as the antimuscarinic results can cause far-reaching adverse effects in this population. Second-generation antipsychotics can likewise be offered for treating behavioral disturbances in dementia. Off-Label usage of second-generation antipsychotics is acquired immunodeficiency syndrome-related dementia.
Substance-induced psychotic disorder: In instances of significant psychosis an additional to substance use, antipsychotics have the right to be offered to control agitation symptoms. Caution is crucial when using first-generation antipsychotics in alcohol withdrawal and phencyclidine intoxication.
Childhood Schizophrenia: current studies have presented the benefit of clozapine in dealing with early-onset schizophrenia.

Other indications

Huntington disease, Parkinson disease, Lesch-Nyhan syndrome, pervasive developmental disorder space some other problems where antipsychotics space an option though that is not the main drug the choice.


This drug is the agent of an option when the patient has actually failed multiple trials of traditional antipsychotic therapies. Clozapine is additionally useful in the therapy of tardive dyskinesia. Indications because that the use of clozapine include treatment-resistant mania, severe psychotic features, obsessive-compulsive disorder, pervasive developmental disorders, childhood autism, Parkinson disease, Huntington disease, and also suicidal patient through schizophrenia or schizoaffective disorder.

Mechanism of Action

The first-generation antipsychotics job-related by inhibiting dopaminergic neurotransmission. Their efficiency is finest when lock block around 72% that the D2 dopamine receptors in the brain. They also have noradrenergic, cholinergic, and histaminergic impede action.

Second-generation antipsychotics work by impede D2 dopamine receptors and serotonin receptor antagonist action. 5-HT2A subtype the serotonin receptor is most commonly involved.


First-Generation Antipsychotics

All dopamine receptor antagonists are available and have the right to be administered in dental form. Except for thioridazine, pimozide, and also molindone, all other first-generation antipsychotics can additionally be offered parenterally. Haloperidol and fluphenazine can be delivered in long-acting depot parenteral form.

Second-Generation Antipsychotics

These deserve to be administered in oral or parenteral forms. Risperidone, olanzapine, aripiprazole, and paliperidone are obtainable as extended-release or long-acting injectable forms. Clozapine, asenapine, and also olanzapine are easily accessible in the sublingual formulation.

Adverse Effects

First-generation antipsychotics (FGAs) are linked with far-reaching extrapyramidal next effects. Anticholinergic adverse effects like dried mouth, constipation, urinary retention are common with low potency dopamine receptor antagonists favor chlorpromazine, thioridazine. The action of H1 histamine impede by First-generation antipsychotics reasons sedation. Chlorpromazine is the many sedating, if fluphenazine, haloperidol, and also pimozide are less sedating. First-generation antipsychotics can also lower the seizure threshold, and chlorpromazine and also thioridazine are an ext epileptogenic than others. Haloperidol can reason abnormal heart rhythm, ventricular arrhythmia, torsades de pointes, and even sudden fatality if injected intravenously. Various other FGAs can reason prolongation that QTc interval, prolonged atrial and ventricular contraction, and also other cardiac conduction abnormalities. Thioridazine has actually a FDA boxed warning for sudden cardiac death. Low-potency FGAs, like chlorpromazine or thioridazine commonly reason orthostatic hypotension. This adverse result caused through alpha-adrenergic block normally occurs when beginning treatment, and also patients often build a tolerance. It is essential to prevent treating hypotension through epinephrine. Leukopenia, thrombocytopenia, and blood dyscrasia are rare side effects of treatment with FGAs. Raised serum prolactin concentrations in addition to galactorrhea, chest enlargement, amenorrhea, impotence in men, and anorgasmia in females are well-known adverse effects because of the action of the dopamine receptor block in the tuberoinfundibular tract. Allergic dermatitis and also photosensitivity can take place with chlorpromazine. Chlorpromazine is additionally associated through blue-gray skin discoloration and benign pigmentation of the lens and also cornea. Thioridazine can cause retinal pigmentation, i beg your pardon can continue even after discontinuing the drug.<6><7><8>

Neuroleptic malignant syndrome is a rare however fatal adverse effect that can occur at any kind of time during treatment with FGAs. The beginning of symptom is over 24 to 72 hours with increased temperature, serious muscular rigidity, confusion, agitation, elevation in white blood cell count, elevated creatinine phosphokinase concentrations, elevated liver enzymes, myoglobinuria, and also acute renal failure. The antipsychotic have to be instantly discontinued, and also dantrolene 0.8 come 2.5 mg/kg every 6 hrs up to 10 mg every day is the medicine of choice. Adequate hydration, cooling, and there must be close security of crucial signs and also serum electrolytes. Though the hazard of neuroleptic malignant syndrome is much more with first-generation antipsychotics, second-generation antipsychotics are likewise known to cause this adverse effect.

Second-generation antipsychotics (SGAs) have actually a reduced risk that extrapyramidal side results as contrasted to first-generation antipsychotics. SGAs are linked with far-ranging weight gain and the advancement of metabolic syndrome. The FDA recommends monitoring an individual and family background of diabetes mellitus, dyslipidemia, weight, and height, waist circumference, blood pressure, fasting plasma glucose, and fasting lipid file for every patients. Risperidone is associated with dizziness, anxiety, sedation, and also extrapyramidal next effects. Paliperidone can cause temperature sensitivity to warm or cold temperatures and also QTc prolongation. Olanzapine has been connected with most generally with weight gain, enhanced appetite, and somnolence. Quetiapine is the the very least likely to reason extrapyramidal side effects. The most typical side impacts of quetiapine space somnolence, orthostatic hypotension, and also dizziness. Ziprasidone has virtually no weight gain yet can cause prolongation that QTc. Aripiprazole is the most usual side impact of agitation, headache, and also akathisia-like restlessness. Asenapine deserve to cause rise in serum prolactin concentrations, load gain, and also prolongation of QTc. Clozapine can cause hypersalivation, tachycardia, hypotension, and anticholinergic side effects. Clozapine is unexplained in that it suppresses dyskinesia. Clozapine can reason clinically necessary agranulocytosis, leukopenia, and also therefore calls for monitoring of white blood cells and absolute neutrophil count. The FDA guidelines suggest monitoring absolute neutrophil count weekly because that the an initial six months and, if normal, have the right to be monitored every two weeks after ~ that. Treatment through clozapine must be stop if absolute neutrophil count drops listed below 1000 cells every cubic millimeter or listed below 500 cells every cubic millimeter in those v benign ethnic neutropenia. Clozapine can additionally cause the rare side result of cardiomyopathy and also myocarditis.

FDA boxed warning: Observational studies imply that similar to second-generation antipsychotics, treatment with first-generation antipsychotics may increase mortality danger in elderly patients v dementia-related psychosis.

Larger doses that antipsychotics increase the danger of adverse medicine effects.

Second-generation antipsychotics lug the FDA boxed warning of raised incidence of punch in yonsi patients with dementia. The reference is to avoid the use of second-generation antipsychotics in addition to other drugs that prolong the QTc interval.

Antipsychotics should be avoided during pregnancy, particularly in the very first trimester, and should be offered only if the benefits outweigh the dangers of treatment. Antipsychotics room secreted in chest milk, and also it is recipient to protect against breastfeeding.


Some antipsychotics can be monitored for a plasma therapeutic range. The is encourage to monitor plasma concentration at a trough, which is at a minimum of 12 hours after the former dose, and best in ~ 20 to 24 hrs after the critical dose. Most antipsychotics do not have a well-defined dose-response curve. 

Haloperidol has a therapeutic range of 2 come 15 ng/ml, chlorpromazine has a range of 30 come 100 ng/ml, and perphenazine has a selection of 0.8 come 2.4 ng/ml.

Clozapine shows a much better treatment an answer at a plasma concentration of 350 micrograms every milliliter or higher.

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Enhancing healthcare Team Outcomes

Antipsychotics room widely used medicines for a variety of mental health disorders. When effective, this drugs do have countless potential side effects. Healthcare workers, functioning as one interprofessional team, need to be aware of the disadvantage effects since they have the right to seriously impact the top quality of life. To prevent the metabolic impacts of these drugs, the patient requirements to receive information concerning lifestyle changes. Continuous exercise, discontinuation that smoking, and eating a healthy and balanced diet room essential. Also, at each clinic visit, the patient"s human body weight, blood cholesterol, blood sugar, and blood pressure must be recorded. If the patience is on clozapine, then consistent monitoring of the white cell counting is required. Only through strictly monitoring can the high morbidity of these drugs it is in limited.<9><10><5>

When the clinician initiates therapy, they should define the treatment to the patient. Nursing have the right to reiterate this education, answer questions, and assess patient progress and adherence to succeeding visits. Lack of medicine adherence have the right to be an important cause of therapy failure. The pharmacist requirements to inspect for every potential drug-drug interactions, and verify proper dosing. A board-certified psychiatric pharmacist can also consult top top the case with the clinician, offering feasible alternatives if treatment does not progress as hoped, e.g., introduce a long-acting dosage form. With these interprofessional interactions, antipsychotic treatment can attain optimal outcomes because that the patient.

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