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 it’s a return of the psychotic symptoms that required treatment initially. This is incredibly difficult to study due to the number and type of people needed, difficulty in blinding the study and ethical concerns. I suspect neither side is absolutely correct about this. [Minnesota drug withdrawal physicians]
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.
Footnotes
* 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.
Respectfully, one can’t quote a textbook on such a vital issue as this.
This is utter baloney. I have been struggling to get off Geodon – it is a powerful drug and a nasty nightmare from hell which ^made^ me ill. I could not live on the drug, and the withdrawals from it are as much hell.
It has MADE me disabled. I am in crisis with little support. Alone.
People struggle for years to quit antidepressants – how much more so would this apply to antipsychotics. Even doctors will advise not to quit quickly. Peer specialist advice would advise not more than 10% per month, and to hold, if not stable, before the next reduction.
This advice is dangerous and should be retracted.
Viz. “ 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.”^”
Hi Natasha,
I don’t really own a website so not sure what to put in that blank on this form…not sure if required field. Anyway, you are awesome with all your research!! Thank you for putting all this info out there for the public to find. I like that a lot…since I a info. addict and I search the internet to figure out my situation. Maybe you can post some places people can go for help or counseling. That is what I am looking for…I have told my family and friends that I need to switch medications and I may not be the same person.
Hi Gabrielle,
You can find mental health services locators on my “Get Help Now” page. https://natashatracy.com/get-mental-illness-help/
– Natasha Tracy
Hi Natasha,
I’ve been taking antipsychotic meds for 10 years and I don’t like taking them at all. I’m currently on Amisulpride (Solian). I haven’t really had a major relapse of my illness, but the problem with discontinuation is that my doctors think any symptoms occurring during withdrawal are coming from the original psychosis. It’s very hard to know who is right here. I don’t really get a lot of support with the problems. If I trust that symptoms will go away, maybe I make a huge mistake and throw my life into a mess again. Then again, it could turn out just fine. I’m not really ready to risk it, but I wish more than anything that I could go without the meds, because they take the joy out of life for me. When I complain about feeling depressed all the time, I am told this, too, is the underlying illness. It just doesn’t seem to make sense to me. Anyway, thanks for your effort with this blog.
Hey, I found this article somewhat comforting to think a person of intelligence would even consider the hypothesis of a long term dependency on anti-psychotics from a non-substance abuse perspective. I am a mentally ill person that suffers from a brain illness not a personality disorder. I have psychological issues but nobody’s perfect. Anyway I have been researching this a great deal since being diagnosed with schizoaffective in 07′. I’ve been administered risperdal, geodon, haldol, Invega, and I’m allergic to Lamictal. These drugs are like psychedelic drugs in a way since they are life changing. My over consumption of psychedelic drugs as a teen most likely caused my illness to develop but I believe these drugs once stopped leave the brain sicker than they previously were. They strip you of your human connection & personality otherwise known as emotions. I believe the parts of the brain they target over time become aggravated by the meds in addition to the nervous/digestive/metabolic system experience what seems like a nuclear meltdown. I am afraid to stop my meds & risk becoming hypomanic or psychotic as each subsequent episode is harder to recover from but I also fear taking these pills for life which seems impossible. Everyday I feel closer to a panic attack when a manic spell or a depressive spell doesn’t sound so bad compared to being a soulless shadow of my former self. I have a pretty high iq without sounding like an arrogant person and I’m afraid of brain damage & life as a senior adult. I don’t want to develop Alzheimer’s or dementia. I am a very active athlete & weight trainer & I know in my heart that these pills stop the normal activity of a healthy body & a healthy mind. I think as I said they actually aggrevate the targeted areas of the brain over time damaging the synaptic nerves. There is a book The Natural Medicine Guide to Bipolar disorder by Stephanie Marohn that tells of methods to cure yourself naturally. Nevertheless I am terrified from past traumatizing experiences in mental hospitals & I am afraid for my life & freedom to stop taking them. Robert Whitaker wrote a book titled Anatomy of an Epidemic that details the realities of mental illness from a non-drug company executive perspective. I have written many journal entries & planned a book about my history. I only hope I can find a cure one day before I end up dead from an unknown cause so some lame psychiatrist can do a half ass piss poor autopsy. It’s like there’s no way of escaping your fate. I’d rather be a hero of medical science than a monster of insane delusion & tragedy but it’s not easy when the field is clouded with lies & the dangers of stigma & persecution are very real. Everyday I feel guilty & I’ve never would never hurt a soul.
Anti-psychotics are not “addictive” ,for a drug to be addictive It has to produce a high a person likes leading them to take it long enough to get dependent.
To use slang, to get “hooked” anti-psychotics don’t have the “hook” needed to be addictive like street drugs.
Dependence is very real after taking antipsychotics for a wile.
Zyprexa or Olanzapine is structurally similar to clozapine, but is classified as a thienobenzodiazepine. Keyword “benzodiazepine” I went through pure hell getting of this stuff. “Tardive psychosis” is very real , I NEVER had psychotic symptoms until withdrawal from this poison called zyprexa.
I took it for 5 months for anxiety and insomnia. When I quit :
All that extra hunger went away and I was left with nausia and daily vomitting for months.
Then the sleep all day feeling turns to insomnia thats fueled by anxiety like I never had before to the point of psychosis. This took 4 days begin.
I had to pace back and forth for hours to deal with this insanity day after day never knowing if it would ever end.
I went through this hell for months because anything was better than continuing to take zyprexa and having no feelings.
Zyprexa was given to me for xanax withdrawal, zyprexa withdrawal is 20 times worse.
Zyprexa should be in the same class as thalidomide.
What a load of rubbish. Seroquell has a street name as it is abused so often; Susie-Q.
Reports of quetiapine(seroquel) abuse have emerged in the medical literature, however, while the drug is usually abused through the crushing and snorting of tablets (insufflation), there have also been reports of intravenous abuse and intravenous co-administration with cocaine.[54] This is commonly referred to as a “Q-Ball”. From wikepedia.
Antipsychotics are the most likely psychotropic to lead to parkinsonism and movement disorders, and yes; like all psychotropics they are dependency forming.
I would encourage people to look up tolerance to anti-psychotics, it exists and is very common.
Please for people just type in antipsychotic into google and look at wikipedia to see are more objective review of antipsychotics.
First of all I want to say what an awesome blog you have. You are really putting your research skills to an excellent purpose and for this I highly commend you. Great post here. I take medication for bipolar disorder and have for many years. I will take it for the rest of my life, having tried to discontinue it three times when I was doing well and causing a disaster to occur. The issue of whether it is addictive or not is a complete non-issue to me. I want to say to people: “Who cares? This has given me back my life! If I have a few less brain cells or a consistent dry mouth it is an extremely low price to pay compared to the alternative…
Elizabeth,
Well thank-you, that is very kind.
“The issue of whether it is addictive or not is a complete non-issue to me. I want to say to people: “Who cares?””
This is true for many. In spite of the fact that it’s clear that taking these medications does not constitute an addiction, you are correct, on some level, it doesn’t even matter.
There’s a commenter here that takes large doses of Seroquel and feels much better on it. What he says is that he doesn’t care if it takes a few years off his life because it means he can enjoy the years he has now.
It would be nice if medication didn’t make us sacrifice anything, but that just ain’t the world in which we live.
– Natasha Tracy
At the mental health clinic I stayed, they were really into prescribing low doses of Seroquel for unipolar depression. Mainly as a sleep aid and to stop obsessive thoughts. I was on 100 mg for a while, it really helped me fall asleep (although I was on Mirtazapine too so it might have been just that) but did nothing against the obsessive and suicidal thoughts. They tried to up it but then I just felt horribly dizzy. So we stopped at some point, going down first to 50, then 0. I don’t think I had any withdrawal, unlike for benzos and SNRIs. So all in all I think for me there was little harm or gain. Still after reading up on this stuff I became somewhat angry for the widely prescribed off-label use of these antipsychotics since side effects can be strong. Especially since I was not told. Do you maybe have any thoughts on this practice? Do you know about studies that show a positive influence of antipsychotics in unipolar depression? I’m just curious…
Hi Leah,
Seroquel (quetiapine) is very common for unipolar depression treatment, as you stated, as a sleep-aid and as a general antidepressant.
Seroquel has been in talks for a few years now to try and get it FDA-approved for depression treatment. The data is there but the increased risk in an antipsychotic over current antidepressants is not considered acceptable given the number of already available treatments (that’s the sense I’m getting).So, yes, Seroquel was used off label, technically.– Turns out this wasn’t the case. See next comment.Aripiprazole (Abilify) is an FDA-approved antipsychotic “indicated for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD).”
Oolanzapine (Zyprexa) and fluoxetine (Prozac) when used in combination is “indicated for the treatment of treatment resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode)”
When used together they are called Symbax.
Those are the only 2 antipsychotics I can think of that have FDA-approval for depression proper. Most of the atypical antipsychotics have study data showing use in depression even if they aren’t approved for it.
So I think it’s quite reasonable to prescribe them and yes, there’s quite a bit of evidence.
That being said, when something is prescribed off label it would be nice if the doctor said so. And yes, I have had the same experience where I’ve been put on antipsychotics with no mention of the serious side effects. I think this lack of transparency is deplorable in most circumstances.
The decision of what to tell the patient and when is a long one and in all honesty, when you’re an inpatient, they tell you less. If you’re an inpatient, you’re in an emergency or you wouldn’t be there. It’s not really the time to be discussing study data. The doctors are trying to stabilize you and get you home. (You might agree or disagree with that.)
The trouble is that later, when there is time and you’re no longer inpatient, no one bothers to take the time to catch you up. Then, you do have time and a chance to make a more informed decision but most doctors don’t bother.
This piece talks about atypicals in treating depression: http://dbt.consultantlive.com/psychiatric-management/content/article/1145628/1488915
This provides you will all sorts of drug data but is not super-up-to-date (tends to only show what the med was initially FDA-approved for and not other approvals) http://www.neurotransmitter.net/drug_reference.html
Hope that helps.
– Natasha Tracy
Leah,
Took me _forever_ to figure this out, but it turns out Seroquel XR _is_ approved for adjunct MDD treatment. So, it’s use for you wasn’t off label. (Seroquel isn’t approved just the XR version is. That’s why it’s so confusing.)
Just writing a post about your topic now.
Sorry for the confusion.
– Natasha
Thanks for the extensive research! Actually I was given a low dose of regular Seroquel first, later a slightly higher dose of XR which only made things worse, so we went back to the regular lower dose. Doesn’t make sense to me why XR would be approved but not the other, but anyway. I guess I will let them off the hook for the off-label thing…
Hi Leah,
You’re welcome :) What can I tell you, I’m a research addict. I have a hard time answering a question unless I’ve verified the answer and (often) have supporting information. I think it’s because I see so much crap on the internet I have no desire to add to it.
The reason the XR version would have approval over the regular is because it’s newer. If you have to spend money on approvals, you do it with the newest patent. And generally, once an XR version comes out everyone switches to it anyway. (Prevents having to take it more than once a day, although not an issue for people taking it primarily for sleep.)
– Natasha Tracy