Novel / Atypical Antipsychotics – The New Stylee Mood Stabilizers

The current atypical, or novel antipsychotics on the US market are:
Risperdal (risperidone)
Zyprexa (olanzapine)
Abilify (aripiprazole)
Geodon (ziprasidone HCl)Seroquel (quetiapine)
Clozaril (clozapine)
In addition to being used to treat schizophrenia and schizoaffective disorders, these medications are being pushed as monotherapy for bipolar disorder, and they are getting FDA approval for such. New atypicals are coming to market with concurrent approval for bipolar and schizophrenia. There’s also a big push to prescribe the atypicals for anxiety/panic to avoid the nasty addiction & abuse problems associated with benzodiazepines. While less effective for most people than SSRIs or benzodiazepines in combating anxiety & panic (but more effective than meds that don’t work at all), sudden withdrawal from long-term use of an atypical antipsychotic can be weird but not really that big a deal. Other than the return of the symptoms it’s treating, of course. That can really suck.

The atypicals work with the receptors of serotonin, dopamine, norepinephrine, histamine and muscarine (and to a lesser extent GABA) in really selective parts of the brain to block hyperactive input. They all work pretty much the same way, except for the first one, Clozaril (clozapine), which is pretty much in a class by itself.
To use a stereo analogy, let’s assume all the crap in your head is like having a radio tuned to a station you don’t like that’s turned up too loud. Both anticonvulsants and antipsychotics work to tune the radio to a preferable station, but they work on the volume in a different manner. The anticonvulsants actually turn down the volume. The antipsychotics work like earplugs, the volume is still turned up, but you can’t hear it so it doesn’t make a difference. It’s a long paragraph per drug to cover each receptor they work with and to what degree, so we’ll skip the details, but at least the drug companies know! This is why they work for bipolar in addition to dealing with anxiety, irrational thoughts, hallucinations and maybe even depression in some cases. This is might also be why, with too high a dose, which for some people could be any amount, they can cause horrendous depression.

If it’s bad enough where you need to take an antipsychotic, there’s usually no question that you need to be taking meds. Plus you need to be seeing a therapist or a counselor. If you’re nuts, you need to see a therapist, and that’s that. The meds are just not enough. If you’re taking these meds for a sleep disorder or any other off-label uses, you should see a counselor to get a better idea of how you need to live your life with whatever disorder you have, because your doctor sure as hell isn’t going to tell you everything you need to know. And regardless of the affliction, you need to belong to a support group to learn what it’s really all about to have whatever you have. For more information on, and reasons why you should be seeing a pro and belong to a support group, take a look at my page on support groups.

Common Side Effects of Novel / Atypical Antipsychotics
Even though it’s class action lawsuit city with the atypical antipsychotics these days because of their side effects, the side effects really aren’t that bad!
Side effects common to all novel / atypical antipsychotics are short-term nausea and other gastric distress, headaches and dizziness. Not so short-term is the sleepiness. Most of the atypicals make you very tired, something you may or may not get over. They’re likely to mess with your dreams, but for good or ill is impossible to predict.
Like the anticonvulsants, the atypical antipsychotics make you photosensitive and can mess with your hormones, usually to a lesser extent on both counts. Risperdal (risperidone) is the hormonal exception, so ladies need to especially watch out with Risperdal (risperidone), as it is notorious for messing with prolactin.

While we’re on the subject of hormones, a large Spanish study has Risperdal (risperidone), the standard antipsychotic Haldol (haloperidol) and Zyprexa (olanzapine) the worst offenders for sexual side effects. They all seem to be dosage-related, so the higher the dosage the worse the sexual dysfunction will be.

The very nature of the drugs are such that they can cause odd effects at times, like extrapyramidal symptoms (EPS), depersonalization and/or derealization; so you do this weird hand-jive, you’re not who you are and nothing is real. Only you get to feel that way with federally approved drugs, and not that questionable mescaline you purchased from some guy you met at a rave the other night. Many people complain of “feeling like a zombie.” Except for the EPS, these other wacky feelings usually pass within a matter of a couple of weeks.
Sadly, the antipsychotics can make one psychotic. It doesn’t happen often, but it does happen. Especially if you’re bipolar and subject to the paradoxical reaction to medications. You really do have to keep a close watch on yourself when you first take them. Fortunately you can just stop taking them at the doses used for anxiety, high-functioning autism, most adjunctive bipolar therapy, and as part of a cocktail for refractory depression. When taken as monotherapy for bipolar and the schizophrenia spectrum they’d have to be reduced in dosage like most other meds.

Or you can talk to your doctor about switching to another one altogether. But if you are bipolar and this has happened more than twice you may as well just give up on the class all together.

EPS / TD / NMS Risk with Novel / Atypical Antipsychotics
You’ll see reference to Extrapyramidal Symptoms, or EPS. They include TD (see below) and a bunch of other fancy medical terms for various uncontrolled movements. EPS can be weird hand movements, like you’re signing in Esperanto. It can mean you’ve become the uberklutz, tripping not only over your own feet but over your own knees. It can mean tremors and twitches and tics and tap dancing. EPS can be temporary, my weird hand-jive and extra klutziness (on top of my natural klutziness) went away after a few weeks. Or EPS can last as long as you take the novel / atypical antipsychotic. The best evidence around, from clinical studies to the stories of people who take these drugs, is that once you stop taking the med, or lower the dosage below the point at which it shows up, the problem goes away. Or you can treat it with an anti-Parkinson’s drug. You have options! While more likely to happen with the standard antipsychotics, and to last longer with them, EPS still happens with the atypicals. I should know! But lowering the dosage took care of my EPS issues. To what extent you’re will to put up with EPS and for how long is between you, your doctor and what symptoms you’re trying to manage with the med in question.

From what I’ve read in various online support groups lowering the dosage is often enough to deal with the issue most of the time, while switching to another med will do it for many of the other times someone has EPS. There are some people who can’t take any antipsychotic because of EPS, but they are a small percentage of the population. In theory it’s impossible to get EPS with Clozaril (clozapine), but there’s always someone who proves to be exceptional to that rule.
So far Seroquel (quetiapine) and Zyprexa (olanzapine) have tested to be the least likely of the popular atypicals (i.e. not Clozaril (clozapine)) to cause EPS. Anecdotal evidence is suggesting that Risperdal (risperidone) is the one most likely to cause EPS. This includes TD.
TD is the absolute worst of the extrapyramidal symptoms. The best evidence is that permanent Tardive Dyskinesia can be avoided if the offending medication is halted, or even the dosage lowered, once the symptoms (weird facial tics and twitches, and uncontrollable tongue rolling and bending) first appear. TD symptoms show up now and then in people who take atypical antipsychotics and really, it’s no big deal. Well, OK, it is sort of a big deal. Lowering the dosage or switching to another antipsychotic is usually all it takes to make the symptoms disappear and the threat of TD vanish. TD is nasty and not to be treated lightly, and your doctor needs to be notified immediately if any symptoms that remotely resemble TD symptoms present themselves. But as long as you’re on top of things you need not fear TD. However doctors do need to discuss it with anyone who is going to be taking antipsychotics.

Case in point – my experience with TD. It came on suddenly. One day Mouse noticed that my tongue seemed to be sticking out of my mouth more when I spoke certain words and that I had some minor facial tics that I wasn’t aware of. The next day my tongue had a mind of its own, I was totally aware of facial tics without having to look in a mirror, and I was blinking like a cartoon owl broadcasting Morse code. Lowering my dosage of Risperdal (risperidone) from 0.5mg a night to 0.25mg reduced the symptoms, but they still flared up now and then. Eventually I had to stop taking a very effective med. The TD was gone for the most part. I still had a bit of a tic in my forehead, but I’m a really poor metabolizer of meds, so maybe the Risperdal (risperidone) was hanging around for a long time, given the 30 hour half-life of the active metabolite for poor metabolizers. Plus tics are side effects of other meds I take, and once you get a side effect going like that, it’ll just hang around if the other meds will make it easier to do so. But it really never went away until I took Seroquel (quetiapine), which along with Zyprexa (olanzapine) has been used to treat the permanent form of TD that is more likely from taking standard antipsychotics. So, really slow metabolism of Risperdal (risperidone) or permanent, if intermittent presentation of one minor TD symptom that didn’t bother me all that much that required another med to deal with? I honestly don’t know.

Did it freak me out? Of course it did! For about an hour. I knew what was going on, I knew how to deal with it. Fortunately I have the luxury of knowing how meds work and not having to leave my house for days at a time. So if something like this happens to you, go ahead and freak out! It’s scary! And Christ on a crutch, to go out in public when that’s happening to you on top of everything else you’re dealing with? It’s one thing when you’re used to dealing with that sort of thing most of your life, but it’s something else entirely when it’s a brand new event in your life. While I personally don’t give a shit about tics and blinking and my tongue going wacky on me when I’m trying to buy groceries, I’m not the rest of the world.
Still, my experience pretty much matches that of others I’ve read. You freak, you talk to your doctor, you switch meds, the symptoms go away.
An extremely rare but potentially deadly side effect is Neuroleptic Malignant Syndrome. While TD is more likely to hit old ladies, NMS is more likely to hit young men. The risk of NMS increases when mixing the standard antipsychotics with lithium. Does the same hold true for the novel / atypical antipsychotics? I have no idea. I can find a case report about it here and there. The case reports I’ve seen has it more likely when mixed with other meds, but it has happened when the drugs are taken by themselves as well. Still, the very threat of NMS makes me uncomfortable with using an atypical antipsychotic for monotherapy to treat bipolar disorder in young men when there are the proven treatments of lithium and anticonvulsants. While the off-label applications for these meds are at dosages so low that there’s even less of of threat of NMS, and with untreated schizophrenia you’re more likely to die if you don’t treat your illness than you would if the threat of NMS were a hundred times greater than it is, my philosophy is why take one more unnecessary risk, along with the other long-term issues of antipsychotics, when you don’t need to?
Early symptoms include fever, rigidity and increased heartbeat. Unlike TD, NMS requires a lot of intervention in addition to cessation of the medication.

Unlike EPS, the chances for NMS, exceedingly rare as they are (I mean, fewer than 100 cases total for all the atypicals) seem evenly spread across the board.

Long-Term Issues with Novel / Atypical Antipsychotics
It’s class-action lawsuit city these days thanks to the first three points. Given how low the risks are, and how these suits make point five worse, one really needs to do a cost/benefit analysis on these lawsuits regarding things like diabetes, pancreatitis and the like.
One thing we’re not really sure of are the long-term effects of these meds. Lithium and the anticonvulsants have been around forever, we know that the anticonvulsants are pretty benign long-term and lithium mainly has the hypothyroidism to look out for. Long-term usage of standard antipsychotics is pretty dodgy. Long-term usage of atypical antipsychotics is, for now, a big unknown. Will long-term use make the chances of permanent EPS, TD or Neuroleptic Malignant Syndrome more likely? Or will the chances remain as low as ever? I wish I knew, as it looks like I’ll be taking Risperdal (risperidone) for a good long time. At least, I thought I was until the TD hit. Dammit. I liked Risperdal! And so did Kassiane, and she had to stop it for the same reason.

So far the worst, and most reported long-term issue is the risk of diabetes. Zyprexa (olanzapine), Clozaril (clozapine) and Seroquel (quetiapine) stack up as the worst in this regard. Risperdal’s (risperidone) status isn’t too clear. Between the weight gain, working your liver really hard, and just messing with your glucose processing, diabetes is a serious threat for anyone who needs to take these meds on a regular basis for a long period of time. If not permanently.

Somewhat related to the above is an increased risk for pancreatitis. 192 instances and 22 deaths as of 2003 out of tens of thousands of people taking these medications. The worst offenders are, in order, Clozaril (clozapine), Zyprexa (olanzapine) and Risperdal (risperidone). If it looks like you’ll be taking on of these meds for at least six months, you should talk to your doctor about regular tests for pancreatitis. You really need to have the tests done if you’re also taking a valproate (Depakote (divalproex acid), or Depakene (valproic acid)) and/or you’re of African descent.

Atypicals can lower your seizure threshold. Not only that, but there are often many drug-drug interactions with anticonvulsants. So if you’re also epileptic you need to be extremely careful when taking these meds. Based upon my own experiences and in gathering information from other people with epilepsy and other conditions that benefited from antipsychotics, the anecdotal evidence points to Risperdal (risperidone) as being the most tolerable for people with a seizure disorder and Seroquel (quetiapine) as being the least tolerable. Mileage will vary, of course.

Probably the biggest long-term issue with the atypical antipsychotics is their cost. They are the most expensive medications in the psychiatric pharmacopoeia. That may be great news for the big pharmaceutical companies, which is a big reason why they are getting pushed for things like monotherapy of bipolar disorder, but that’s not such good news for the consumer.

Taking Novel / Atypical Antipsychotics
What is a big deal is to avoid alcohol with antipsychotics. I didn’t when I was first on Risperdal and I think some occasional heavy drinking contributed to my nervous breakdown on or about my birthday in February of 2002. Mixing alcohol and benzodiazepines can be fatal. Mixing alcohol and anticonvulsants is weird. Mixing alcohol and most modern antidepressants is generally not a big deal. But mixing alcohol and antipsychotics can seriously mess with your head, sometimes with long-lasting results. Here is an example of what a couple of glasses of wine and a low dosage of Seroquel (quetiapine) can do to someone in distress and looking for support on an Internet support group. Normally this person can type proficiently:

siorry jmy popst lioikds l;ielk i am druikn

i dont driglk

i am toooo tired ot tyo;pw

i dolnt droinkkkkk

mky yese asre all mlessed ujp form anothner drugnnnnnnnand i haove a sevfer

healtdcalcl]]\

myua got toe er donot nfelel l ewelll at allllllllll

strfated birth donltroel pil;ls as fewa daYs ago

for metopauose

tye agian tomoerowow

Then, twenty minutes later:

theklank s brina

i have nbmb halnds and at heatdacah e

form new pillllllllllls well lsee dr tabout that domtoorrow

what isss keoppera?

caleed nursre aboutj mmmmy porblem wriantnng and wiath the bumv b’handedss

wils se dorctor tomeorw

headabke very bnead anow to gbed now

head burts

beok soom

gonit wondw worry pplaese

The withdrawal has been likened to taking small amounts of psychedelic drugs. Whether that is a good or bad thing is up to individual experience. Others get rebound symptoms for a day or two, sometimes longer and that’s about it. Of course, that’s for issues where it’s OK to stop taking meds at some point, like panic/ anxiety disorders. The big problem is that the bipolar and the schizophrenic are the worst about stopping their meds because they think they’re cured when their symptoms stop. Wrong answer! Your symptoms stop because the meds are working. As of the early 21st century there are no cures for these disorders, just management of symptoms. The good news is you can just start right back up on the atypicals and get back to where you were in controlling your symptoms.
One great thing about antipsychotics is that you can take them as required (or PRN in medical shorthand). Feeling just a bit too anxious or manic? Try some Risperdal (risperidone) or Zyprexa (olanzapine) instead of increasing your normal amount of benzos or mood stabilizers / anticonvulsants. Once you feel stable, you can just stop taking the extra antipsychotics. Let me stress the extra part. If an antipsychotic is your primary medication and you’re feeling just great you have to keep taking your maintenance dosage, whatever that may be. Now you can discuss with your doctor about taking a lower dosage and seeing how that works out. These meds are very flexible when it comes to dosages. Go up, go down, in the long run it turns out to be OK as they are far less picky than the anticonvulsants.
Even though I was skeptical at first and thought the real reason for pushing antipsychotics for bipolar and anxiety was money, I’m starting to come around to them. On the bipolar side of things several act as true mood stabilizers for some people, helping with both mania and depression. They are perfect for the non-compliant, which defines the schizophrenic and bipolar, as some have long half-lives and they work just fine if you stop taking them and start up again. The combination of atypical antipsychotics and antidepressants is being shown to be the best thing since sex to combat bipolar depression and refractory unipolar depression.
Conversion for atypicals. This is just an approximation, in case you need to switch from one of the popular atypical antipsychotics to another quickly because of adverse effects. Obviously 3mg of Abilify (aripiprazole) will not sedate you like 100mg of Seroquel (quetiapine). I’ve placed them from the most to least potent to give you an idea of what the range is like. Note that Risperdal (risperidone) is 200 times as potent as Seroquel (quetiapine). Depending on how your symptoms are acting up it’s between you and your doctor if you want to stop taking one on Friday and start taking another on Saturday (or whenever you can schedule time off for a med change). While switching SSRIs isn’t as big a deal, it’s just a matter of some drug clearances (i.e. you won’t clear out the meds as quickly when you have two of them in your system at the same time), having two antipsychotics in your system at the same time does make it somewhat more likely that you could experience EPS or even NMS. These work only for the starting dosages. These things aren’t exactly linear, therefore at the higher dosages they don’t exactly map out. So if you’re switching from a high dosage of one to another your doctor is probably writing you a prescription that makes a lot a sense. If you want to try to do the math yourself, see the NIMH Psychoactive Drug Screening Program. If you ask me how to use that site, you’re not qualified to use it.
0.5mg Risperdal (risperidone) = 2.5mg Zyprexa (olanzapine) = 3mg Abilify (aripiprazole) = 20mg Geodon (ziprasidone HCl) = 100mg Seroquel (quetiapine) = you only want to take Clozaril (clozapine) if you’re really messed up and nothing else is going to work. OK, Clozaril (clozapine) works on your brain in a completely different way as well, so there’s not an easy dosage equivalent. Plus it has some very specific uses that are different from the other atypicals.
The same applies to switching between a standard/typical antipsychotic and an novel/atypical. They do the same sort of thing, but in slightly different ways. People do it all the time, I just don’t know an easy equivalent. Plus you really want to have whatever you’re switching from out of your system before you start what you’re switching to, unless the side effects are completely horrible and your symptoms are even worse. As above, you just increase the risk of EPS or even NMS with the two types of antipsychotics in your system. It’s all a matter of figuring out which is more dangerous, the very small risk of EPS or NMS, or the chance of your doing something very dangerous to yourself or others if you’re not medicated enough.

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