Side Effects

Extrapyramidal

These side effects are due to D2 receptor blocks in, or affecting, the extrapyramidal motor area of the brain. There are two main disturbances that can occur; acute dystonias, which are reversible, and tardive dyskinesia, which is often permanent. These side effects are mainly found with the typical class of antipsychotics, as the atypical classification was originally assigned to the compounds which showed reduced motor side effects. Some other side effects are also associated with extrapyramidal blocks, such as increased hormone prolactin levels.

Acute Dystonias

In the first few weeks of antipsychotic treatment acute dystonias may present themselves, which can cause involuntary twisting or repetitive movements such as muscle spasms, protruding tongue, etc., or abnormal postures. Acute dystonias are reversible upon ceasing treatment. It is believed that the effects come about via block of the nigrostriatal dopamine pathway, which is consistent with the fact that atypical drugs (which are more selective for other dopamine pathways) do not produce acute dystonias. Other drugs, such as muscarinic acetylcholine receptor (mAChR) blockers can reduce acute dystonias as the dopamine receptor and mACh receptor systems act in opposite ways.

Tardive Dyskinesia

Around 20-40% of patients treated with typical antipsychotics develop tardive dyskinesia after months or years of treatment, or with high doses. It is a permanent condition causing involuntary and repetitive movements of the face, tongue, trunk and limbs. This can be highly disabling for the patient. The condition often gets worse when ceasing to take antipsychotics, and treatment is usually unsuccessful. It is commonest in patients over 50. The video below shows a man demonstrating the effects of tardive dyskinesia. He has trouble walking and a strong hand tremor.


Other extrapyramidal effects are associated with: akathisia (restlessness), parkinsonism (rigidity and tremors), tachycardia (increased heart rate), hypotension (decreased blood pressure), impotence, lethargy, seizures, intense dreams or nightmares, and hyperprolactinaemia.

Prolactin

Hyperprolactaemia is increased levels of a hormone, prolactin, in the blood. In women this can cause decreased oestrogen, leading to infertility and a decrease, irregularity or total halt of menstruation. Increased prolactin can also cause production of breast milk, and loss of libido. In males hyperprolactaemia can cause decreased libido, gynecomastia (male breast formation), infertility and impotence.

Metabolic

Many of the newer atypical drugs tend to produce weight gain, and it is thought that this is due to blocking of serotonin receptors. Diabetes mellitus and diabetic ketoacidosis, which can both be fatal, have also been associated with atypical antipsychotics, especially olanzapine.

Anticholinergic

The phenothiazines, and some other, antipsychotics can also block muscarinic acetylcholine receptors (mAChRs), which can lead to unwanted side effects including; increased intraocular pressure, blurring of vision, dry eyes and mouth, constipation and urinary retention. On the other hand, blocking mAChRs can reduce extrapyramidal side effects as said above, due to the mAChRs and dopamine receptors working in opposition.

Haematologic

Clozapine has a 1-2% risk of incidence of leucopenia, which is a potentially fatal decrease in the number of circulating white blood cells. The incidence is much lower with other antipsychotics (1 in 10 000). Risk of agranulocytosis, a related condition involving a reduction in other blood cells, including neutrophils, is also increased in clozapine patients.

Other Side Effects

Antipsychotic malignant syndrome is a rare but serious reaction, and is highly dependent on the individual. After around two weeks of administration of the drug the patient can present with muscle rigidity, rapid rise in body temperature, and cognitive effects such as confusion and delerium. This can be fatal, with 10-20% of patients dying from heart or kidney failure. 

Older typical antipsychotics can produce mild obstructive jaundice, which can be recovered from quickly with a change of antipsychotic drug. The symtoms are usually  dark urine, pale faeces and the patient may itch.

Urticarial skin reactions, such as hives, can be common, but usually are mild and can resolve quickly. This is possibly due to modification of the histamine pathways. Some patients also show hightenened sensitivity to UV light.


Related Links

Links relating to the side effects of antipsychotic medication:


Rethink Mental Health Charity Antipsychotics Side Effects Page:

http://www.rethink.org/living_with_mental_illness/treatment_and_therapy/medication/antipsychotics/side_effects_of.html

Information on the main side effects of antipsychotic medication.


Mind Mental Health Charity "Making Sense of Antipsychotics" Page:

http://www.mind.org.uk/Information/Booklets/Making+sense/antip.htm#What_are_the_side_effects

Good source of information regarding most aspects of antipsychotic medication.


Wikipedia Antipsychotics page:

http://en.wikipedia.org/wiki/Antipsychotic

Some useful information on the side effects of antipsychotics.