# Antipsychotics --- **Antipsychotics** are a type of [[psychotropics|psychotropic]] drug that alleviate the symptoms of psychosis such as hallucinations and delusions. People can do reasonably well on antipsychotics, but the side effects are often severe and sometimes even stigmatizing. Some people are on antipsychotics long term, and other times they can be used for acute [[mania]] (or any acute agitation regardless of cause) to get someone to chill out. Some other uses are things like: - psychosis caused by substances or substance withdrawal - adjunct treatment of severe unipolar depression - irritability and challenging behaviors associated with autism or intellectual disability - impulsivity and irritability associated with personality disorder, [[dementia]] and [[delirium]] - delusional disorders Antipsychotics do not cause tolerance or dependence. If someone needs a higher dose than they had been getting, (which is relatively common) it's because their disease is getting worse, not that the medicine isn't working anymore. ## Generations 1-3 When the first antipsychotics were developed they completely changed the game for treatment for people with psychosis, and fundamentally changed our understanding of mental illness. Before the advent of chlorpromazine (brand name: Thorazine) we were essentially in the stone age. That said, there still remains pretty significant challenges with the treatments we have now, and hopefully psychiatry in the future will look back on what we have today with the same feelings. - **First generation** (sometimes called **typical antipsychotics**) were the first drugs that *meaningfully* improved people's psychotic symptoms with a medication. - they are giant [[dopamine]] sledgehammers, which can successfully treat psychosis but also cause their own problems - have serious side effects ([[extrapyramidal side effects|EPS]], [[metabolic syndrome]], etc.) - Examples: - [[phenothiazines]] (The -zines and Haldol) - Haldol, Thorazine - **Second generation** (sometimes called **atypical antipsychotics**) were developed in the late 80's-90s (know olanzapine) [[atypical antipsychotics]] - still a dopamine sledgehammer, but with modular effects with serotonin (i.e. a finer control on them) - they have same side effect profile, but some are less severe - When they first came out we thought they didn't have side-effects, but they just didn't have people on them for long time. For example, they still causes metabolic syndrome at the same rate, if not more severely - Examples: - clozapine, risperidone, lurasidone, quetiapine, ziprasidone - **Third generation** antipsychotics are the most modern iteration of antipsychotics - they create a partial dopamine blockade...so they're like a *smaller* sledgehammer - side effect profile is generally better - even weight gain is less - lower incidence of EPS/TD ## Spotlight on **Clozapine** Clozapine is the only antipsychotic shown to be more effective than the others - reduces the risk of suicide - rare side effect of (rapid onset) [[agranulocytosis]] - 8 per 10,000, or less - requires blood drawn on regular schedule, weekly at first - underutilized in the US, due to the red tape (which is difficult for your average person to navigate, let alone some one with psychoses) - "No blood, no drug". If they don't get lab draws at a certain frequency they are not allowed to dispense the drug. - only about 5% of the US population that could use it is on clozapine, the drug that works the best ## Adverse Reactions Antipsychotics have serious side-effects that are sometimes permanent even if the patient stops taking the med. For the most part we are choosing antipsychotics based on tolerability, because they all have about a similar efficacy in the long run. Almost all antipsychotics cause: - weight gain - this can be like 60-100 pounds over 6 months - increases hunger, decreased feeling of satiety, genuine cravings for carby food - not particularly dose dependent - sedation - hormonal reactions - reduced libido - retrograde ejaculation - gynecomastia - amenorrhea - [[extrapyramidal side effects]] - **anticholinergic effects** - dry mouth - dry eyes/blurry vision - constipation - actually a really big issue - urinary retention - **Neuroleptic Malignant Syndrome** is a rare but serious side effect. It often occurs with young patients, physically healthy, being exposed to a new drug for the first time. It is treatable, as long as you catch it in time. - unstable vitals - elevated temperature - usually tachycardia - muscle rigidity - tightening of the jaw and head, with the head tilted back - strange eye movements - altered mental status - bear in mind this person will probably be experiencing psychosis, so we are looking for alterations from *their* baseline. Changes in orientation, level of alertness (people with psychosis are generally alert and oriented). ## Examples - Olanzapine - mania - Aripiprazole - mania - Lurasidone - depressive episodes in Bipolar 1 - Quetiapine - mania - Risperidone - mania - Ziprasidone - mania - Thorazine - psychosis - off label: intractable hiccups, painkiller ___