Psych meds 101: Antipsychotics

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Therapeutic uses

Needless to say the primary use of antipsychotic medications is in the treatment of psychosis. There are a number of other uses, though, and the atypicals (I’ll get to that soon) are more versatile than the older drugs. Atypical antipsychotics have an important role to play as mood stabilizers in bipolar disorder and to augment antidepressant regimens in major depressive disorder. They may also be used for anxiety, and quetiapine is a common example of this. Sedating antipsychotics such as quetiapine and methotrimeprazine may be used for sleep. Haloperidol, a typical antipsychotic, is used in the treatment of delirium, a rapid-onset disturbance in cognition and orientation.

Mechanism of action

Antipsychotics work by blocking D2 dopamine receptors. This impacts four major dopamine pathways in the brain, producing the therapeutic effect as well as side effects:

  • mesocortical: this affects areas of the prefrontal cortex (the most evolutionarily advanced part of the brain) associated with cognition and mood
  • nigrostriatal: this pathway is associated with movement
  • tuberoinfundibular: this pathway regulates the hormone prolactin

Side effects

While there is no way to predict which specific person is going to experience which particular side effects, in general medication side effect profiles are based on the types of receptors they interact with.

Movement-related symptoms

Extrapyramidal symptoms (EPS) occur most commonly with typical antipsychotics. These are named for an area of the brain that is part of the nigrostriatal dopamine-signalling. Excessively blocking dopamine in this region produces movement-related side effects, including tremor, rigidity, and akathisia (restlessness). Anticholinergic medications such as benztropine can help to reverse these symptoms, due to an inverse relationship between the neurotransmitters acetylcholine and dopamine in this part of the brain.

Neuroleptic-induced deficit syndrome

This is a fancy name for causing apathy and related symptoms similar to negative symptoms of schizophrenia. This can result from blocking dopamine receptors in the mesocortical pathway, and primarily occurs with typical antipsychotics.

Prolactin-related effects

Dopamine blockade in the tongue-twisting tuberoinfundibular pathway can increase levels of the hormone prolactin, which can result in some distressing side effects. It can affect both sex drive and sexual function, and can also cause gynecomastia (development of breast tissue in men). In general atypicals are less likely to cause this, although risperidone tends to carry a higher risk than other atypicals.

Metabolic effects

The atypicals win out over the typicals in many senses, but a major downside is that they do carry a risk for metabolic syndrome, including weight gain, increased cholesterol, and increased risk of diabetes. This may be related to activity at histamine and 5HT2c serotonin receptors. The big three are clozapine, olanzapine, and (to a lesser extent) quetiapine. Aripiprazole and ziprasidone do not tend to be associated with weight gain.

Sedation

This can be related to effects on histamine, muscarinic, and alpha adrenergic receptors. Individual medications vary in terms of which of these receptors they do or don’t effect, so there is a lot of variability in sedating effect.

Anticholinergic effects

The cholinergic signalling system is responsible for resting and digesting activities. When antipsychotics disrupt this, the result can be things like dry mouth and constipation. On a more positive note, this can decrease the likelihood of experiencing EPS. Again, there is a lot of variation from medication to medication as to anticholinergic activity.

Drug-specific details

Quetiapine (atypical)

Quetipine affects serotonin and norepinephrine signalling in addition to its action on dopamine, and this likely contributes to its beneficial effects on mood. The dose range varies widely, and for good antipsychotic effect the dose needs to be at the higher end of the range, approaching 1000mg/day.

Olanzapine (atypical)

Olanzapine is beneficial for mood. It has a low risk of EPS.

Risperidone (atypical)

Of the atypicals, risperidone is the most likely to cause EPS and prolactin-related side effects. Risperidone is metabolized by the body into paliperidone, which carries a somewhat lower risk of side effects.

Aripiprazole (atypical)

Aripiprazole has a unique mechanism of action. It’s a partial agonist at D2 receptors, meaning it tries to create something along the lines of the Goldilocks just-right bowl of porridge. It’s not sedating, and can actually help boost people’s energy. It’s not associated with weight gain. For all that it sounds like a pretty good drug, when I tried it several years ago I found my mood actually got worse.

Clozapine (atypical)

Clozapine can be a wonder drug for people whose psychotic symptoms are resistant to other medications. It is the only antipsychotic that has been shown to decrease the risk of suicide in schizophrenia. However, it can be problematic in terms of side effects. It can increase the risk of seizures. It can cause drooling, which can be quite bothersome for some people. It can cause a dangerous drop in white blood cells, so bloodwork is required every 1–4 weeks. When starting clozapine, there is a small risk of an inflammatory reaction in the heart called myocarditis. It’s definitely not a first line medication, but sometimes you really do need to bring out the big guns.

Typical antipsychotics

Examples include loxapine, haloperidol, zuclopenthixol, and flupenthixol. The latter three are often given as long-acting injections, although there are more alternatives now as a number of atypicals have become available for injection.

Long-acting injections

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In conclusion…

I hope that I haven’t confused you or totally turned you off of antipsychotics. Personally I’ve taken quetiapine for years and will continue to take it for many more. Antipsychotics can do a world of good, and I would say the most important thing is to work with your treatment provider to find what works best for you.

Written by

Mental health blogger | MH Nurse | Living with depression | Author of 3 books, latest is Managing the Depression Puzzle | mentalhealthathome.org

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