Antipsychotics

Introduction to Antipsychotics

Antipsychotics have been in use since 1950, when Chlorpromazine (the first drug with specific antipsychotic effects) was synthesized. The indications for use of antipsychotics include short-term management of anxiety, management of disturbed behaviour, schizophrenia, mania, toxic delirium, brain damage and agitated depression. Some atypical antipsychotics such as Quetiapine are also prescribed 'off-label' in the treatment of depression. Antipsychotics are commonly referred to as being either first or second generation. The terms typical and atypical are also used to describe first and second generation antipsychotics. The therapeutic effects of first generation/typical antipsychotics are thought to arise from blockade of dopamine (D2) receptors.

The effects of typical antipsychotics are not confined to specific dopamine receptor types or dopaminergic pathways. This can lead to negative effects such as movement disorders and raised prolactin levels. Second generation antipsychotics target a wider range of receptors. They tend to be have more distinctive therapeutic and negative effects than second generation antipsychotics. However, different antipsychotics often share some potential negative effects regardless of their typical or nontypical status. Antipsychotics are often invaluable in the effective treatment of psychosis, as well as other conditions including depression. However they have no recreational value, along with potentially debilitating and fatal negative effects. Their use is best confined to prescribed and supervised treatment.

Using Antipsychotics

Ways of administration

Antipsychotic drugs are administered orally and by intramuscular injection. There is a risk of sudden cardiac death where antipsychotics are used intravenously. Intramuscular injections of antipsychotics bypass first metabolism. High levels of physical activity also increase blood supply to muscles and therefore the rate of absorption. This means that when these drugs are administered in emergencies the intramuscular dose should be smaller than the oral dose of the drug in question.

Longer acting depot injections are often used for ongoing treatment. These increase the likelihood of extrapyramidal effects, a group of forms of movement disorder. Second generation/atypical antipsychotic depot preparations are less likely to cause extrapyramidal effects than first generation antipsychotics.

Depot injections are given every one to four weeks, by deep intramuscular injection usually in the upper outer quadrant of the gluteous maximus. A technique known as Z-tracking is used; before injecting the skin is pulled to one side. As the needle is withdrawn and the skin is released the layers of skin, subcutaneous fat and muscle move back to their original positions. This means that the injection site does not leak out the contents of the depot, as the hole created does not line up through the layers of muscle, subcutaneous fat and skin.

Effects of Antipsychotics

Combinations with Antipsychotics

Antipsychotic medications are often given in combination with drugs which are used for the prophylaxis of bipolar affective disorder/manic-depressive psychosis. Prophylactics used in combination with antipsychotics include:

• Valproic Acid and Sodium Valproate, used for the prophylaxis of the manic episodes which form part of a cycle of bipolar affective disorder.
  
• Carbamazepine, which is best used with specialist supervision. Indications include rapid cycles of bipolar affective disorder and a lack of response to other prophylactic medication.
  
• Lithium salts (Lithium Carbonate and Lithium Citrate), used in the prophylaxis and treatment of mania and prevention of bipolar affective disorder. Lithium salts are also used in combination with antidepressants to manage treatment-resistant depression in bipolar affective disorder. The therapeutic to toxic range of lithium serum concentrations is small, close monitoring of these is critical in safe use.

Antidepressants are used to treat depression in the context of bipolar affective disorder. Antidepressants may be contraindicated in those with a recent history of mania, rapid changes in mood and rapid cycles of bipolar affective disorder. Combined use of antidepressants and antipsychotic drugs may be indicated in those experiencing depression with symptoms of psychosis. Treatment should be supervised by a clinical specialist.

Benzodiazepines can be helpful during early treatment in managing agitation or disturbed behaviour. These drugs are not suitable for long-term treatment given their addictive potential and the possibility of benzodiazepine withdrawal. Diazepam is given intravenously in the treatment of life-threatening acute dystonic reactions.

Antimuscarinic drugs (also referred to as anticholinergics) are used to manage the effects of central over-availability of acetycholine which can arise from dopamine blockade. Antimuscarinics indicated in the treatment of drug-induced Parkinson's disease include Procyclidine, Orphenadrine and Trihexyphenidyl.

Antihistamines (including Diphenhydramine) are employed in a medical setting to reduce muscle contractions occurring during acute dystonic reactions.

Different Uses for Antipsychotics

The dangers of Antipsychotics

Forms of Antipsychotics

Antipsychotics are split into two classes: Typical and Atypical. Typical antipsychotics also known as major tranquilizers were the first to hit the market, some examples being Thorizine (chlorpromazine) and Haldol (haloperidol). Atypicals are more widely prescribed currently due to a more favorable safety profile and more tolerable side effects; some examples are: Seroquel (quetiapine), Zyprexa (olanzapine), Geodon (ziprazidone), Abilify (apiprazole) and Rispridal (risperdone), among others.

History of Antipsychotics

More Antipsychotics Sections

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References

British National Formulary February 2013.
Down on the Pharm': All About Acute Dystonic Reaction. Hayes C.M. 2012.