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Clozaril (clozapine). The oldest of the atypicals, it is rarely prescribed because of the need for weekly blood tests for agranulocytosis (not enough white blood cells) and the significant chance of seizures and changes to heart rhythms. Anyone prescribed Clozaril has to go into a national registry and it can be prescribed only by doctors who have filled out the appropriate paperwork to be certified to prescribe it.  

The up side is there hardly any chance of getting TD or any extrapyramidal symptoms (EPS) from this med, and may even be a potential treatment for TD,[1] and it doesn't even mess with your prolactin (no leaky tits!) the way most other antipsychotics do. That and there's nothing in the psychosis spectrum of conditions that Clozaril can't fix, or at least make suck less.  Why?  It's the most broad-spectrum antipsychotic on the market.  It blocks practically everything in your brain with moderate-to-strong blockades of dopamine receptors 1 through 4, six serotonin receptors, two alpha-noradrenergic receptors, one muscarinic receptor and the ever-popular H1 histamine receptor.  Zyprexa is the only drug that comes close to what Clozaril does.

Clozaril is hands down the toughest choice to make if you've run out of options and really, really need an antipsychotic.  It's bad enough that 2% of people taking it get agranulocytosis and just reading this page probably made you gain a pound.  Besides the threat to the elderly being treated off-label for dementia with any antipsychotic, Clozaril has four unique, unlikely-to-rare, but potentially life-threatening side effects.  Agranulocytosis, seizures, myocarditis - inflammation of the heart muscle, which is so rare Clozaril doesn't even show up as a cause for myocarditis in most places and the threat goes away after a month, and an extreme form of orthostatic hypotension.  The last one is sudden super-low blood pressure and usually happens only if you're taking another sedating med like a benzo.  Lots of meds have it as a side effect, but it's always along the lines of "stand up too fast, feel like passing out."  The Clozaril + other drug version can just make you suddenly sleepy, and you never wake up.  The scariest part is it usually happens if you skip taking your meds for two or more days then take your usual high dosage.  Medication compliance is extremely important with Clozaril.

Freakiest rare side effects: complete loss of speech, and the lovely combo of libido increase and priapism. The initial dosage is 12.5 mg once or twice daily and then adding increments of 25-50 mg/day, if well-tolerated, to achieve a target dose of 300-450 mg/day by the end of 2 weeks for schizophrenia. For other ailments you can increase the dose by 100 mg over the course of one or two weeks and see how it goes. The maximum dosage is 500 mg for outpatients, 900 mg for inpatients. Clozaril has a half-life of 12 hours. Novartis.

Full US Prescribing Information

New Zealand Data Sheet (for doctors)

UK Summary of Product Characteristics (for doctors)

UK Patient Information Leaflet

Australia PI Sheet (for doctors)

Australia Consumer Medicine Information

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