Safety of First-Generation Antipsychotics Like Haloperidol

Safety of First-Generation Antipsychotics Like Haloperidol

First-generation antipsychotics (typical antipsychotics, neuroleptics) have been around since the 1950s, but how safe are first-generation antipsychotics like haloperidol? One doctor, Henry A. Nasrallah, MD, suggests that haloperidol and its likenesses should be retired as first generation antipsychotics are not safe for the brain (he and the literature contend). Are first-generation antipsychotics like haloperidol safe or possibly neurotoxic?

Why Were Second-Generation Antipsychotics Created?

First generation antipsychotics were quite effective and Dr. Nasrallah himself attests to haloperidol’s “unquestionable efficacy in treating delusions and hallucinations.” However, first-generation antipsychotics also had a nasty side effect profile and often caused movement disorders that were very unpleasant, distressing and sometimes permanent.

Second-generation antipsychotics (atypical antipsychotics) were designed with movement disorders in mind and, indeed, movement disorders have been drastically reduced in patients using second-generation antipsychotics. At the time, it was also thought that second-generation antipsychotics were more efficacious but studies have shown this not to be the case. First- and second-generation antipsychotics have approximately equal efficacy. (There are certainly nasty side effects to second-generation antipsychotics, too, but more on that another day.)

Is Haloperidol Dangerous and Neurotoxic?

According to Dr. Nasrallah, haloperidol and older-generation antipsychotics are, absolutely, dangerous and neurotoxic. Twenty-eight studies he lists report various destructive effects of first-generation antipsychotics, especially haloperidol. He identifies these categories of the molecular mechanisms of neurotoxicity:

  • First-generation antipsychotics like haloperidol have been in use 60 years but are first-generation (typical) antipsychotics safe? Is haloperidol safe?Apoptosis – the death of cells
  • Necrosis – the death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply.
  • Decreased cell viability
  • Inhibition of cell growth
  • Increased caspase activity (the “death spiral”)
  • Impaired glutamate transport
  • Mitochondrial damage

Dr. Nasrallah contends that these drugs would never be allowed by current day Food and Drug Administration (FDA) standards and that if these same effects were seen in other realms (i.e., not invisible) the FDA would likely move to ban them altogether. (But no one cares about crazy* peoples’ brains anyway.)

Is Haloperidol Safe? Should You Ever Take a First-Generation Antipsychotic?

People are prescribed different medications for different reasons and there may be justifiable reasons to prescribe a first-generation antipsychotic to someone. I’m not sure what that would be (see below) given the preponderance of evidence of neurotoxicity, but everyone is different and I’m sure there are cases I haven’t thought of as I’m not a doctor.

However, in light of this evidence, I would suggest that haloperidol is not safe and that safer alternatives, like the atypical antipsychotics which have been shown to “exert neuroprotective properties, such as inducing neurogenesis and increasing neurotrophic factors” should always be investigated to a great degree before putting your brain in harm’s way of a neurotoxic drug. (By the way, you might want to keep those neuroprotective factors in mind the next time someone tells you that antipsychotics are killing your brain.)

At the very least, if you, or someone you love, is taking a first-generation antipsychotic, it’s at least worth a serious conversation with your doctor so you can evaluate your, specific, pros and cons.

Edit: Since writing this I have consulted with a psychiatrist on the matter and he says that he still prescribes first-generation antipsychotics in two cases. In case one, it may happen inpatient temporarily in the case of florid psychosis. In case two, some people simply don’t respond to second-generation antipsychotics but do positively respond to first-generation ones. And if there’s one thing I know to be true it’s that all our brains are very different so this, in fact, does make sense.

For more information and references, please see Current Psychiatry 2013 July;12(7):7-8., Haloperidol clearly is neurotoxic. Should it be banned?. (You’ll likely need a free login to see it.)

* Before you start throwing tomatoes at the screen, this is a snide way of denoting how society views those with mental illness. I’m not suggesting people with mental illnesses are, in fact, crazy.

Banner image by ZngZng (Own work) [CC BY-SA 3.0], via Wikimedia Commons

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