In the first of this series I discussed antidepressants and addiction. Some people contend antidepressants are addictive; however, not only is the term “addiction” not defined medically, the use of antidepressants does not generally match the symptoms of any defined substance use disorder either. (More information on substance abuse and substance dependence.)
This time antipsychotics are up to bat. Are antipsychotics addictive? Are people dependent on antipsychotics? Do antipsychotics cause withdrawal?
What Are Antipsychotics?
Antipsychotics are medications designed to treat psychosis, typically in schizophrenia. Antipsychotics block both dopamine and serotonin receptors in the brain although typical and atypical antipsychotics do it a little differently.
Typical antipsychotics are the older generation of antipsychotics and include antipsychotics like haloperidol and chlorpromazine. Atypical antipsychotics are second generation antipsychotics and include medications like olanzapine and quetiapine.
Aripiprazole and other partial dopamine agonists, (they increase dopamine levels in the brain) are sometimes called third generation antipsychotics due to a different mechanism of action but this point is debatable.
Can You Abuse Antipsychotics?
Antipsychotics have been widely shown to be perceived as unpleasant and have a high discontinuation rate. Animals trained to press a bar to avoid being given an antipsychotic will do so 90% of the time.^ For these reasons, people do not take antipsychotics for “pleasure” they take them to get well. A pattern of antipsychotic abuse can almost never be established.*
Can You Become Dependent on Antipsychotics?
Many people (typically those with schizophrenia and bipolar disorder, although some with unipolar depression as well) are dependent on antipsychotics to function. However, this does not rise to the level of a substance dependence disorder as a substance dependence disorder requires the appearance of tolerance and taking increasing amounts of the drug. The therapeutic effects of antipsychotics show almost no evidence of tolerance (in other words, you stay on the same therapeutic dose over time), but tolerance to some side effects is present.
Antipsychotics and Withdrawal
While there are clearly not the requisite symptoms to categorize antipsychotic use as a substance use disorder, withdrawal symptoms are known to appear. Withdrawal from antipsychotics is a hotly-debated issue.
Some doctors believe a psychosis that develops during antipsychotic withdrawal is a withdrawal symptom (for some patients) and is evidence of the brain’s physical dependence on the drug; while others say this is a return of the psychotic symptoms that required treatment in the first place. This is incredibly difficult to study due to the numbers of people you would need in a heterogeneous population, difficulty in blinding the study and ethical concerns. I suspect neither side is absolutely correct about this.
What We Know About Antipsychotics and Withdrawal
Here is what we know from studies:
Perceptions of Antipsychotic Medication
- The risk of dependency was assessed as ‘low’ by GP’s (80%), in contrast to only 18% of the general population.
- A majority of the general population recommended discontinuation of the antipsychotic for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%).
- “As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects.” (Study link.)
Brain Volume Changes after Withdrawal
Schizophrenia (and other illnesses like bipolar disorder and unipolar depression) are known to shrink brain volume. Recently, a study came out asserting long-term antipsychotic use shrinks brain volume also. This is a highly contentious issue (as they all seem to be).
A study came out shortly after the one above stating antipsychotics protect people with schizophrenia from brain loss. Regarding patients in first-episode schizophrenia:
- Decrease in those on and off antipsychotics in cerebral gray matter and caudate nucleus volume over time was significantly more pronounced in patients relative to controls.
- Decreases in the nucleus accumbens and putamen volumes during the interval in patients who discontinued antipsychotic medication.
- Increases in nucleus accumbens and putamen volumes were found in patients who continued their antipsychotics.
- This might suggest discontinuation reverses effects of atypical medication.
Antipsychotics and Dependency
OK, I admit, that’s not a lot of data. I did searches on Pubmed but only covered about the last ten years. I suspect a lot of study on this was done earlier. And keep in mind, most withdrawal effects are seen upon abrupt discontinuation from the antipsychotic (i.e. not a slow taper) and are dose dependent.
One textbook I have states
“Physical dependence, if it occurs at all, is rare. There are reports of muscular discomfort, exaggeration of psychotic symptoms and movement disorders, and difficulty in sleeping when some antipsychotics are suddenly withdrawn, but such effects are not normally seen even after years of use at normal doses. It is possible that the failure to notice withdrawal symptoms is due to the extremely slow excretion of the drug from the body.”^
Next time I’ll look at benzodiazepines which, while I personally like, have a not-so-nice story around addiction.
* There are extremely rare cases where antipsychotic abuse occurs. This has not been shown in studies but at least one case study has been written about it.
^ McKim, William, “Drugs and Behavior Sixth edition” Person Prentice Hall. 2007.