Antipsychotic - Side Effects

Side Effects

Antipsychotics are associated with a range of side effects. It is well-recognized that many people stop taking them (around two-thirds even in controlled drug trials) due in part to adverse effects. Extrapyramidal reactions include acute dystonias, akathisia, parkinsonism (rigidity and tremor), tardive dyskinesia, tachycardia, hypotension, impotence, lethargy, seizures, intense dreams or nightmares, and hyperprolactinaemia. Side effects from antipsychotics can be managed by a number of different drugs. For example, anticholinergics are often used to alleviate the motor side effects of antipsychotics. Some of the side-effects will appear after the drug has been used only for a long time.

Some studies have found decreased life expectancy associated with the use of antipsychotics, and argued that more studies are needed. In Feb. 2011, a minor loss of brain tissue was reported in schizophrenics treated with antipsychotics. Brain volume was negatively correlated with both duration of illness and antipsychotic dosage. No association was found with severity of illness or abuse of other substances. An accompanying editorial said: "The findings should not be construed as an indication for discontinuing the use of antipsychotic medications as a treatment for schizophrenia. But they do highlight the need to closely monitor the benefits and adverse effects of these medications in individual patients, to prescribe the minimal amount needed to achieve the therapeutic goal to consider the addition of nonpharmacological approaches that may improve outcomes." Continuous use of neuroleptics has been shown to decrease the total brain volume by 10% in macaque monkeys.

In "healthy" individuals without psychosis, doses of antipsychotics can produce the so-called "negative symptoms" (e.g. emotional and motivational difficulties) associated with schizophrenia.

From a subjective perspective, antipsychotics heavily influence one's perceptions of pleasurable sensations, causing a severe reduction in feelings of desire, motivation, pensive thought, and awe. This does not coincide with the apathy and lack of motivation experienced by the negative symptoms of schizophrenia. Detrimental effects on short term memory, which affect the way one figures and calculates (although this also may be purely subjective), may also be observed on high enough dosages. These are all the reasons why they are thought to affect "creativity". Also, for some individuals with schizophrenia, too much stress may cause "relapse".

Following are details concerning some of the side effects of antipsychotics:

• Antipsychotics, particularly atypicals, appear to cause diabetes mellitus and fatal diabetic ketoacidosis, especially (in US studies) in African Americans.
• Antipsychotics may cause pancreatitis.
• The atypical antipsychotics (especially olanzapine and clozapine) seem to (due to occupancy of the histamine receptor) cause weight gain more commonly than the typical antipsychotics. The well-documented metabolic side effects associated with weight gain include diabetes, which can be life-threatening.
• Antipsychotics increase the likelihood of a fatal heart attack, with the risk of death increasing with dose and the length of time on the drug.
• Clozapine also has a risk of inducing agranulocytosis, a potentially dangerous reduction in the number of white blood cells in the body. Because of this risk, patients prescribed clozapine may need to have regular blood checks to catch the condition early if it does occur, so the patient is in no danger.
• One of the more serious of these side effects is tardive dyskinesia, in which the sufferer may show repetitive, involuntary, purposeless movements (that are permanent and have no cure) often of the lips, face, legs, or torso. It is believed that there is a greater risk of developing tardive dyskinesia with the older, typical antipsychotic drugs, although the newer antipsychotics are now also known to cause this disorder.
• A potentially serious side effect of many antipsychotics is that they tend to lower an individual's seizure threshold. Chlorpromazine and clozapine, in particular, have a relatively high seizurogenic potential. Fluphenazine, haloperidol, pimozide and risperidone exhibit a relatively low risk. Caution should be exercised in individuals that have a history of seizurogenic conditions such as epilepsy, or brain damage.
• Neuroleptic malignant syndrome, in which the drugs appear to cause the temperature regulation centers to fail, resulting in a medical emergency, as the patient's temperature suddenly increases to dangerous levels.
• Dysphoria.
• Drug-induced parkinsonism due to dopamine D2 receptor blockade may mimic idiopathic parkinsonism. The typical antipsychotics are more prone to cause this, compared to the atypical antipsychotics.
• Sexual dysfunction, which may rarely continue after withdrawal, similar to Post-SSRI sexual dysfunction.
• Dystonia, a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.
• Hyperprolactinaemia. The breasts may enlarge and discharge milk, in both men and women due to abnormally-high levels of prolactin in the blood. Prolactin secretion in the pituitary is normally suppressed by dopamine. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin.
• There is evidence that exposure may cause demyelinating disease in laboratory animals.
• Following controversy over possible increased mortality (death) related to antipsychotics in individuals with dementia, warnings have been added to packaging.

Some people suffer few apparent side effects from taking antipsychotic medication, whereas others may have serious adverse effects. Some side effects, such as subtle cognitive problems, may go unnoticed.

There is a possibility that the risk of tardive dyskinesia can be reduced by combining the anti-psychotics with diphenhydramine or benzatropine, although this remains to be established. Central nervous system damage is also associated with irreversible tardive akathisia and/or tardive dysphrenia.