Side effects of Atypical Antipsychotics

1.

Elsevier ClinicalKey Drug Class Overview

Content last updated: March 2, 2020.

Adverse Reactions / Side Effects Table Adverse Reactions / Side Effects | Aripiprazole | Aripiprazole lauroxil | Asenapine | Brexpiprazole | Cariprazine | Clozapine | Iloperidone | Lumateperone | Lurasidone HCl | Olanzapine | Paliperidone | Paliperidone palmitate | Pimavanserin | Quetiapine Fumarate | Risperidone | Ziprasidone Hydrochloride | Ziprasidone Mesylate ---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|--- drowsiness | 3 - 23% | 3 - 23% | 3 - 53% | 2 - 5% | 5 - 11% | 39 - 46% | 8 - 15% | 13 - 24% | 11 - 17% | 6 - 48% | 1 - 26% | 1 - 26% | Reported | 18 - 57% | 5 - 63% | 8 - 31% | 8 - 31% akathisia | 2 - 13% | 2 - 13% | 1 - 11% | 4 - 14% | 6 - 23% | 3% | 1.7 - 4.4% | Reported | 6 - 22% | 3 - 27% | 3 - 17% | 3 - 17% | | <5.4% | <11% | <10% | <10% dizziness | 3 - 10% | 3 - 10% | 3 - 11% | <5% | 3 - 7% | 19 - 27% | 10 - 20% | 5% | 4 - 6% | 1 - 18% | 1 - 6% | 1 - 6% | | 9 - 18% | 3 - 16% | 3 - 16% | 3 - 16% hypercholesterolemia | Reported | Reported | <8.7% | Reported | Reported |

xerostomia | 4 - 5% | 4 - 5% | 1 - 3% | Reported | 2 - 5% | 6% | 8 - 10% | 6% | 2 - 5% | 2 - 22% | <3% | <3% | | 7 - 44% | <10% | <5% | <5% fatigue | 2 - 17% | 2 - 17% | 3 - 14% | <5% | 1 - 10% | 2% | 3 - 6% | 3% | 3% | 2 - 14% | <4% | <4% | Reported | 3 - 14% | 1 - 31% | | hyperprolactinemia | <0.1% | <0.1% | <2.6% | Reported | Reported | | 26 - 35% | Reported | Reported | 30 - 47% | >10% | >10% | | 3.6% | >10% | Reported | Reported sinus tachycardia | 2% | 2% | <3% | Reported | 2% | 25% | 3 - 12% | | >1% | 3% | <14% | <14% | | 1 - 8% | 1 - 3% | 2% | 2% constipation | 2 - 11% | 2 - 11% | 4 - 7% | <3% | 2 - 7% | 14 - 25% | | | | 4 - 11% | <5% | <5% | 4% | 6 - 11% | 5 - 17% | <9% | <9% elevated hepatic enzymes | 0.1 - 0.9% | 0.1 - 0.9% | <2.5% | | 1% | 1% | 8% | 2% | | 1 - 28% | Reported | Reported | | 1 - 6% | Reported | 0.1 - 1% | 0.1 - 1% headache | <27% | <27% | 9 - 12% | <9% | 14% | 7% | 5% | | | 8 - 17% | 4 - 15% | 4 - 15% | | 17 - 21% | <21% | 3 - 18% | 3 - 18%

16% hypercholesterolemia | Reported | Reported | <8.7% | Reported | Reported | Reported | 1.1 - 3.6% | 8 - 10% | Reported | 2.8 - 57.6% | <11% | <11% | | 7 - 18% | 4.3 - 6.3% | Reported | Reported hyperglycemia | <17.6% | <17.6% | <11.4% | Reported | 2 - 4% | Reported | Reported | Reported | Reported | 0.9 - 26% | 2.5 - 11% | 2.5 - 11% | | 1.4 - 2.6% | 0.8 - 12.6% | 0.1 - 1% | 0.1 - 1% hypertriglyceridemia | Reported | Reported | 1.9 - 15.2% | Reported | Reported | Reported | <10.1% | 5% | Reported | 9.2 - 70.7% | 1.3 - 13% | 1.3 - 13% | | 8 - 22% | 2.5 - 2.7% | Reported | Reported pseudoparkinsonism | 0.1 - 4% | 0.1 - 4% | 1 - 2% | Reported | 3 - 21% | <1% | 0.2 - 0.3% | Reported | <17% | <14% | <14% | <14% | | <5.5% | <28% | >1% | >1% weight gain | 2.2 - 26.3% | 2.2 - 26.3% | 2 - 14.7% | 3 - 8% | 2 - 8% | 4% | 1 - 9% | Reported | >3% | 5 - 31% | 3 - 19% | 3 - 19% | | 8 - 23% | 8 - 32.6% | 2.4 - 20% | 2.4 - 20% xerostomia | 4 - 5% | 4 - 5% | 1 - 3% | Reported | 2 - 5% | 6% | 8 - 10% | 6%

The potential for metabolic adverse reactions varies significantly among atypical antipsychotics. Among the most consistent findings in all of atypical antipsychotic research is that weight gain, hypertriglyceridemia, and risk of insulin resistance and type 2 diabetes are greatest with clozapine and olanzapine. Quetiapine and risperidone have also been associated with weight gain, but of lesser magnitude. Some agents (e.g., aripiprazole, lumateperone, lurasidone, ziprasidone) appear to have a lower potential for adverse metabolic effects. American Psychiatric Association treatment guidelines and others recommend routine monitoring of weight, waist circumference, serum lipids, and fasting glucose in all patients receiving atypical antipsychotics[28945]. [49637][49638][49642][49645][31510][49649][64885]

Adverse drug reactions (ADRs) and toxicities are the single most important determinant of drug choice within the class. Interestingly, both somnolence and insomnia are very common ADRs with most atypical antipsychotics. Although sexual side effects are common, atypical antipsychotics are significantly superior to first-generation antipsychotics. Constipation, dizziness, dry mouth, and postural hypotension are other common ADRs[49637]. [49638][31510][49649][49656]

2.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 3, 2024.

Adverse Reactions Among the most frequent adverse events associated with the use of seroquel is weight gain, which can contribute to metabolic adverse reactions associated with atypical antipsychotic therapy. Atypical antipsychotics have been associated with metabolic changes. These metabolic changes include blood glucose increases, dyslipidemia, and weight gain. In clinical trials of immediate-release seroquel for all indications studied in adults, a weight gain of at least 7% of body weight occurred in 8% to 23% of seroquel-treated patients. In clinical trials for extended-release seroquel, weight gain of at least 7% of body weight occurred in 10% of those receiving active drug. In clinical trials of immediate-release seroquel for schizophrenia or the manic phase of Bipolar disorder in children and adolescents, a weight gain of at least 7% of body weight occurred in 12% to 21% of seroquel-treated patients. In a long-term extension trial in pediatrics, the mean increase in body weight was 4.4 kg, and 18.3% of patients gained at least 7% of their body weight when adjusted for normal growth. Other effects occurring more frequently with seroquel than placebo included appetite stimulation (2% to 12%) and decreased appetite (2%). Anorexia was reported in at least 1% of patients during premarketing evaluation of seroquel and weight loss occurred in 0.1% to 1% of patients.

3.

Food and Drug Administration (DailyMed).

Publish date: March 5, 2023.

Warnings And Cautions However, some patients may require treatment with Risperidone for Extended-Release Injectable Suspension despite the presence of the syndrome. 5.5 Metabolic Changes Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia and Diabetes Mellitus Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics including risperidone. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics, including risperidone, should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including risperidone, should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including risperidone, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.

Adverse Reactions Blood and lymphatic system disorders: anemia, neutropenia Cardiac disorders: tachycardia, atrioventricular block first degree, palpitations, sinus bradycardia, bundle branch block left, bradycardia, sinus tachycardia, bundle branch block right Ear and labyrinth disorders: ear pain, vertigo Endocrine disorders: hyperprolactinemia Eye disorders: conjunctivitis, visual acuity reduced Gastrointestinal disorders: diarrhea, vomiting, abdominal pain upper, abdominal pain, stomach discomfort, gastritis General disorders and administration site conditions: injection site pain, chest discomfort, chest pain, influenza like illness, sluggishness, malaise, induration, injection site induration, injection site swelling, injection site reaction, face edema Immune system disorders: hypersensitivity Infections and infestations: nasopharyngitis, influenza, bronchitis, urinary tract infection, rhinitis, respiratory tract infection, ear infection, pneumonia, lower respiratory tract infection, pharyngitis, sinusitis, viral infection, infection, localized infection, cystitis, gastroenteritis, subcutaneous abscess Injury and poisoning: fall, procedural pain Investigations: blood prolactin increased, alanine aminotransferase increased, electrocardiogram abnormal, gamma-glutamyl transferase increased, blood glucose increased, hepatic enzyme increased, aspartate aminotransferase increased, electrocardiogram QT prolonged, glucose urine present Metabolism and nutritional disorders: anorexia, hyperglycemia Musculoskeletal, connective tissue and bone disorders: posture abnormal, myalgia, back pain, buttock pain, muscular weakness, neck pain, musculoskeletal chest pain Nervous system disorders: coordination abnormal, dystonia, tardive dyskinesia, drooling, paresthesia, dizziness postural, convulsion, akinesia, hypokinesia, dysarthria Psychiatric disorders: insomnia, agitation, anxiety, sleep disorder, depression, initial insomnia, libido decreased, nervousness Renal and urinary disorders: urinary incontinence Reproductive system and breast disorders: galactorrhea, oligomenorrhea, erectile dysfunction, sexual dysfunction, ejaculation disorder, gynecomastia, breast discomfort, menstruation irregular, menstruation delayed, menstrual disorder, ejaculation delayed Respiratory, thoracic and mediastinal disorders: nasal congestion, pharyngolaryngeal pain, dyspnea, rhinorrhea Skin and subcutaneous tissue disorders: rash, eczema, pruritus generalized, pruritus Vascular disorders: hypotension, orthostatic hypotension Additional Adverse Reactions Reported with Oral Risperidone The following is a list of additional adverse reactions that have been reported during the clinical trial evaluation of oral risperidone, regardless of frequency of occurrence: Blood and Lymphatic Disorders: granulocytopenia Cardiac Disorders: atrioventricular block Ear and Labyrinth Disorders: tinnitus Eye Disorders: ocular hyperemia, eye discharge, eye rolling, eyelid edema, eye swelling, eyelid margin crusting, dry eye, lacrimation increased, photophobia, glaucoma Gastrointestinal Disorders: abdominal pain upper, dysphagia, fecaloma, abdominal discomfort, fecal incontinence, lip swelling, cheilitis, aptyalism General Disorders: thirst, feeling abnormal, gait disturbance, pitting edema, edema, chills, discomfort, generalized edema, drug withdrawal syndrome, peripheral coldness Immune System Disorders: drug hypersensitivity Infections and Infestations: tonsillitis, eye infection, cellulitis, otitis media, onychomycosis, acarodermatitis, bronchopneumonia, respiratory tract infection, tracheobronchitis, otitis media chronic Investigations: body temperature increased, heart rate increased, eosinophil count increased, white blood cell count decreased, hemoglobin decreased, blood creatine phosphokinase increased, hematocrit decreased, body temperature decreased, blood pressure decreased, transaminases increased Metabolism and Nutrition Disorders: polydipsia Musculoskeletal, Connective Tissue, and Bone Disorders: joint swelling, joint stiffness, rhabdomyolysis, torticollis Nervous System Disorders: hypertonia, balance disorder, dysarthria, unresponsive to stimuli, depressed level of consciousness, movement disorder, hypokinesia, parkinsonian rest tremor, transient ischemic attack, cerebrovascular accident, masked facies, speech disorder, loss of consciousness, muscle contractions involuntary, akinesia, cerebral ischemia, cerebrovascular disorder, neuroleptic malignant syndrome, diabetic coma, head titubation Psychiatric Disorders: blunted affect, confusional state, middle insomnia, listlessness, anorgasmia Renal and Urinary Disorders: enuresis, dysuria, pollakiuria Reproductive System and Breast Disorders: vaginal discharge, retrograde ejaculation, ejaculation disorder, ejaculation failure, breast enlargement Respiratory, Thoracic, and Mediastinal Disorders: epistaxis, wheezing, pneumonia aspiration, dysphonia, productive cough, pulmonary congestion, respiratory tract congestion, rales, respiratory disorder, hyperventilation, nasal edema Skin and Subcutaneous Tissue Disorders: erythema, skin discoloration, skin lesion, skin disorder, rash erythematous, rash papular, hyperkeratosis, dandruff, seborrheic dermatitis, rash generalized, rash maculopapular Vascular Disorders: flushing Discontinuations Due to Adverse Reactions Schizophrenia Approximately 11% (22/202) of Risperidone for Extended-Release Injectable Suspension-treated patients in the 12-week double-blind, placebo-controlled schizophrenia trial discontinued treatment due to an adverse event, compared with 13% (13/98) who received placebo.

4.

Food and Drug Administration (DailyMed).

Publish date: July 5, 2023.

Warnings And Cautions 5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring ( 5.4 ) Tardive Dyskinesia: Discontinue if clinically appropriate ( 5.5 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain ( 5.6 ) Hyperglycemia/Diabetes Mellitus: Monitor glucose regularly in patients with and at risk for diabetes ( 5.6 ) Dyslipidemia: Undesirable alterations in lipid levels have been observed in patients treated with atypical antipsychotics ( 5.6 ) Weight Gain: Weight gain has been observed with atypical antipsychotic use. Monitor weight ( 5.6 ) Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation ( 5.7 ) Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope ( 5.8 ) Leukopenia, Neutropenia, and Agranulocytosis: have been reported with antipsychotics including aripiprazole.

5.

Uçok A, Gaebel W. World Psychiatry : Official Journal of the World Psychiatric Association (WPA). 2008;7(1):58-62. doi:10.1002/j.2051-5545.2008.tb00154.x.

Publish date: February 5, 2008.

This paper reviews the available evidence concerning the side effects of atypical antipsychotics, including weight gain, type II diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract. Some recommendations about how to prevent and manage these side effects are also provided. It is concluded that atypical antipsychotics do not represent a homogeneous class, and that differences in side effects should be taken into account by clinicians when choosing an antipsychotic for an individual patient.