The side effects reportedly associated with the various<unk> s vary and are medication-specific. Generally speaking,<unk> s are widely believed to have a lower likelihood for the development of tardive dyskinesia than the<unk> s. However, tardive dyskinesia<unk> ly develops after long-term (possibly decades) use of<unk> s. It is not clear if<unk> s, having been in use for a relatively short time, produce a lower incidence of tardive dyskinesia. Among the other side effects that have been suggested is that<unk> s increase the risk of cardiovascular disease. Kabinoff et al. found that the increase in cardiovascular disease is seen regardless of the treatment received, and that it is instead caused by many different factors such as lifestyle or diet. Sexual side effects have also been reported when taking<unk> s. In males<unk> s reduce sexual interest, impair sexual performance with the main difficulties being failure to ejaculate. In females there may be abnormal menstrual cycles and infertility. In both males and females the breasts may become enlarged and a fluid will sometimes ooze from the nipples. Sexual adverse effects caused by some<unk> s are a result of an increase of prolactin. Sulpiride and Amisulpiride, as well as Risperdone and paliperidone (to a lesser extent), cause a high increase of prolactin. In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of<unk>  use among elderly patients with dementia. The FDA advisory was associated with decreases in the use of<unk> s, especially among elderly patients with dementia. Subsequent research reports confirmed the mortality risks associated with the use of both conventional and<unk> s to treat patients with dementia. Consequently, in 2008 the FDA issued although a black box warning for classical neuroleptics. Data on treatment efficacies are strongest for<unk> s. Adverse effects in patients with dementia include an increased risk of mortality and cerebrovascular events, as well as metabolic effects, extrapyramidal symptoms, falls, cognitive worsening, cardiac arrhythmia, and pneumonia. Conventional<unk> s may pose an even greater safety risk. No clear efficacy evidence exists to support the use of alternative psychotropic classes (e.g. antidepressants, anticonvulsants).<unk> s may also cause anhedonia. Drug-induced OCD Many different types of medication can create/induce pure OCD in patients that have never had symptoms before. A new chapter about OCD in the DSM-5 (2013) now specifically includes drug-induced OCD.<unk> s (second-generation<unk> s), such as olanzapine (Zyprexa), have been proven to induce de-novo OCD in patients. Tardive dyskinesia All of the<unk> s warn about the possibility of tardive dyskinesia in their package inserts and in the PDR. It is not possible to truly know the risks of tardive dyskinesia when taking<unk> s, because tardive dyskinesia can take many decades to develop and the<unk> s are not old enough to have been tested over a long enough period of time to determine all of the long-term risks. One hypothesis as to why<unk> s have a lower risk of tardive dyskinesia is because they are much less fat-soluble than the<unk> s and because they are readily released from D2 receptor and brain tissue. The<unk> s remain attached to the D2 receptors and accumulate in the brain tissue which may lead to TD. Both<unk>  and<unk> s can cause tardive dyskinesia. According to one study, rates are lower with the<unk> s at 3.9% per year as opposed to the<unk> s at 5.5% per year. Metabolism Recently, metabolic concerns have been of grave concern to clinicians, patients and the FDA. In 2003, the Food and Drug Administration (FDA) required all manufacturers of<unk> s to change their labeling to include a warning about the risks of hyperglycemia and diabetes with<unk> s. It must also be pointed out that although all<unk> s must carry the warning on their labeling, some evidence shows that<unk> s are not equal in their effects on weight and insulin sensitivity. The general consensus is that clozapine and olanzapine are associated with the greatest effects on weight gain and decreased insulin sensitivity, followed by risperidone and quetiapine. Ziprasidone and aripiprazole are thought to have the smallest effects on weight and insulin resistance, but clinical experience with these newer agents is not as developed as that with the older agents. The mechanism of these adverse effects is not completely understood but it is believed to result from a complex interaction between a number of pharmacologic actions of these drugs. Their effects on weight are believed to mostly derive from their actions on the H1 and 5-HT2C receptors, while their effects on insulin sensitivity are believed to be the result of a combination of their effects on body weight (as increased body mass is known to be a risk factor for insulin resistance) and their antagonistic effects on the M3 receptor. Some of the newer agents, however, such as risperidone and its metabolite paliperidone, ziprasidone, lurasidone, aripiprazole, asenapine and iloperidone, have clinically insignificant effects on the M3 receptor and appear to carry a lower risk of insulin resistance. Whereas clozapine, olanzapine and quetiapine (indirectly via its active metabolite, norquetiapine) all antagonise the M3 receptor at therapeutic-relevant concentrations. Recent evidence suggests a role of the α1 adrenoceptor and 5-HT2A receptor in the metabolic effects of<unk> s. The 5-HT2A receptor, however, is also believed to play a crucial role in the therapeutic advantages of<unk> s over their predecessors, the<unk> s. A study by Sernyak and colleagues found that the prevalence of diabetes in<unk>  treatments was statistically significantly higher than that of conventional treatment. The authors of this study suggest that it is a causal relationship the Kabinoff et al. suggest the findings only suggest a temporal association. Kabinoff et al. suggest that there is insufficient data from large studies to demonstrate a consistent or significant difference in the risk of insulin resistance during treatment with various<unk> s. Comparison table of adverse effects Generic Name Weight gain Metabolic Effects EPS High prolactin Sedation Hypotension / Orthostasis QTc prolongation Anti-ACh effects Other adverse effects Amisulpride - - - Seizures, suicidal ideation Aripiprazole - - Seizures (0.1-0.3%), anxiety, rhabdomyolysis, pancreatitis (<0.1%), agranulocytosis (<1%), leukopenia, neutropenia, suicidal ideation, angioedema (0.1-1%) Asenapine - Immune hypersensitivity reaction, angioedema, suicidal ideation Blonanserin - - Clozapine Seizures (3-5%), agranulocytosis (1.3%), leukopenia, pneumonia, respiratory arrest, angle-closure glaucoma, eosinophilia (1%), thrombocytopenia, Stevens–Johnson syndrome, myocarditis, erythema multiforme and abnormal peristalsis Iloperidone - - Suicidal ideation (0.4-1.1%), syncope (0.4%) Lurasidone - - - - Agranulocytosis, seizures (<1%), elevated serum creatinine (2-4%) Melperone - / / - Agranulocytosis, neutropenia and leukopenia Olanzapine Acute haemorrhagic pancreatitis, immune hypersensitivity reaction, seizures (0.9%), status epilepticus, suicidal ideation (0.1-1%) Paliperidone - - Agranulocytosis, leukopenia, priapism, dysphagia, hyperprolactinaemia, sexual dysfunction Perospirone ? ? ? - Insomnia in up to 23%, CPK elevation neuroleptic malignant syndrome Quetiapine - Agranulocytosis, leukopenia, neutropenia (0.3%), anaphylaxis, seizures (0.05-0.5%), priapism, tardive dyskinesia (0.1-5%), suicidal ideation, pancreatitis, syncope (0.3-1%) Remoxipride - - - - ? - There is a risk of aplastic anaemia risk which is what led to its removal from the market. Risperidone - Syncope (1%), pancreatitis, hypothermia, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, hyperprolactinaemia, sexual dysfunction, thrombotic thrombocytopenic purpura, cerebrovascular incident (<5%), tardive dyskinesia (<5%), priapism, neuroleptic malignant syndrome (<1%), gynecomastia, galactorrhea Sertindole - - - - Sulpiride - - Jaundice Ziprasidone - - Syncope (0.6%), dysphagia (0.1-2%), bone marrow suppression, seizure (0.4%), priapism Discontinuation The British National Formulary recommends a gradual withdrawal when discontinuing<unk> s to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time. There is tentative evidence that discontinuation of<unk> s can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.
Atypical antipsychotic
Atypical antidepressant
Tricyclic antidepressant
Tetracyclic antidepressant
Heterocyclic antidepressant
Typical antipsychotic
Second-generation antidepressant
Antipsychotic