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Other mood stabilizing agents: now they are looking at lamigatrine and gabapentin. I don’t think those are established enough to the point where I would expect to see them on a Board exam. But some psychiatrists are using them for bipolar disorder. Calcium channel blockers: back when they were having that race for the number one, I was talking about, the calcium channel blockers were kind of a contender and I think what happened was there was no money in getting a calcium channel blocker approved. So nobody did the studies to prove it. But they used to say that things like Verapamil were good for treating bipolar disorders. You never hear that anymore. Refractory cases, you can try ECT.
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All right, medications used for side effects, anti EPS drugs: benztropine, diphenhydramine, traxophenodryl and chlorcyclizine. Amantadine. How many of you think of amantadine as anticholinergic? Or somewhat anticholinergic. I get varying responses to that. It certainly is not a primary anticholinergic drug the way benztropine, Cogentin, is. But a lot of people think it is somewhat anticholinergic. Propanolol is not an anticholinergic but it’s good for acathisia, good for trauma. Cholinergics, in the bad old days, you’d start somebody on Haldol, because they’d be walking around like this after they started the Haldol, and then you’d give them Cogentin to help with the Parkinsonism. And they they’d still be walking around, a little more fluidly, but they tell you, “I can’t urinate, I have dry mouth.” Why is that? Because the Cogentin had anticholinergic side effects and so now you have to combat the side effects of the side effect drug, and you can do that with methanacol, pilocarpine eye-drops, physostigmine for anticholinergic overdose.
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Agents used for ADHD: Dextroamphetamine, methamphetamine, pemoline, which is Cylert. There is a black box warning on Cylert though. Which you can’t use it first line, I guess, because of the liver problem. Modafinil is new. You guys know more about it than I do. I know virtually nothing about it. I think it has something to do with GABA, but I know nothing beyond that. Stimulants are used in ADHD, narcolepsy and depression. Use in weight loss has been controversial. If they say on the Boards, “What’s an acceptable use for methylphenidate?” ADHD definitely, narcolepsy definitely, depression arguably – it’s not FDA approved, you know but a lot of these elderly people are in a nursing home and they are just depressed and you need something to just sort of kick-start them. Or they are on a rehab unit. That can help and I think that’s accepted in psychiatry. How about weight loss? Probably not accepted as part of mainstream medicine. There was a time when it might have been. But if I were taking the Boards I would say no, I don’t think so. But there’s the controversy. There’s people who do nothing but weight loss who will tell you, “You know, modern medicine, organized medicine, what it is is if you keep these people on these drugs for years and years and do it consistently and do it right, you will see that the weight loss is still effective.” Conventional wisdom, my way of thinking, is that I think along the same lines as you guys do and that’s the way I would answer on the Boards. But I do think there is a school of thought that they are acceptable for weight loss. So I’m just saying there has been some controversy. Certainly, I think my state does not approve them for weight loss. I think in my state, Michigan, you can only use them by law for ADHD and narcolepsy.
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Drugs used in bipolar disorder: lithium. Very good for mania but also very effective in treating depression in bipolar patients. Hard to tolerate the effects of GI, alopecia, weight gain, ataxia, acne, polyuria, polydipsia. It takes a while to work, unlike Depakote which you can kind of load the person up. Classically considered to cause cardiac malformations, Ebstein’s anomaly. That was sort of a classic thing. What happens if you give a pregnant woman this drug, what do you get? What happens if you give a pregnant woman lithium? Ebstein’s anomaly. What about Tegretol? Probably craniofacial. That’s what I would answer on Boards. What about cheap Depakote online, valproic acid? Probably neural tube. That’s what I would answer. They need periodic blood monitoring. Cardiac affects of lithium requires EKG monitoring. T-wave inversion, a lot of side effects. Neuro-therapeutic index: remember what therapeutic index is? Here’s how much it takes to kill 50 rats and here’s how much it takes to treat 50 rats. You give 100 rats this drug and at what point do you get the LD 50 where they die? Really what you want is a very wide therapeutic index. In other words, it only takes 10 mg to treat you but it takes 10,000 mg to overdose you. Lithium is not that way, it’s very narrow. It takes this much to treat you but a little bit more can cause side effects and sometimes even death. Very toxic. You can get elevated lithium levels with some diuretics, with diminished salt intake and with NSAID’s. Can get decreased lithium levels with excessive caffeine intake. Somebody is on a psychiatric unit, they are drinking four pots of coffee before they come in, or two pots of coffee a day before they come in. Suddenly they come onto your non-caffeinated psychiatric unit. What happens? Their lithium level goes up because they are not drinking all that caffeine anymore.
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Valproic acid: when I was, early in my training, there was a race. It was like a Coke, Pepsi thing. Who was going to be the number one bipolar drug. Lithium of course had the championship, they had the throne, but these other contenders really wanted to take it away. The contenders were valproic acid and Tegretol. I’ll tell you what happened. The people who make valproic acid were very aggressive in marketing it, advertising it, and proving to the FDA that it was good for bipolar disorder. They did such a good job it sort of eclipsed lithium as a first line treatment. Typically considered inferior to lithium for treating the depressive phase. One advantage is that it can be loaded. You know the side effects; lethargy, alopecia, tremor, hepatotoxicity in kids. You need periodic blood monitoring. Particularly good for rapid cycling. If somebody is a rapid cycling bipolar disorder, they go from mania to depression, mania to depression, very quickly, Depakote or valproic acid is your drug of choice.

Carbamazepine: kind of took the third line seat, as history showed. Good for mania but it has its own side effects: neurological symptoms, elevation of liver enzymes, blood dyscrasias, you all know it promotes its own metabolism. You need to monitor the drug level enzymes. Causes low sodium.

“… man, I feel much better.” It’s like having two beers. You know, a beer or two. Those cells, those neurons are not depolarizing. You cannot panic. If I give you a six-pack of Stroh’s right now I’m not going to be able to make you anxious, no matter what I do. Nothing I say. You are going to be just mellow and sort of subdued. And so it is with these drugs. They are used to right here, right now, quick effects and they are kind of spoiled. Because you try to put them on BuSpar or something like that, especially the ones that are getting a little buzz, like off of Valium, it just doesn’t work well.
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Lets talk about other agents. Chloral hydrate. Older than dirt. You watch these old movies and you’ve got this old private detective and you’ve got this blonde slinking around in this dress, and she says, “Oh, let me get you a drink.” And she takes the drink back into the other room and she makes him a Mickey Finn. What she does is she takes gin and she puts chloral hydrate into it, and then the guy drinks it and he wakes up on the floor, and the movie goes on from there. That was the old Mickey Finn. Barbiturates: meprobamate. I hate that stuff, that meprobamate. People tolerate to it like in six weeks, then it’s no good anymore and you can’t get them off it. You hardly see it any more. I think there are two companies now, I think Equanil and Miltown. Still manufactured, I’m not sure why. Barbiturates, you guys use them for seizures. The anesthesiologists, of course, use it for induction. Psychiatrists do not like barbiturates. This is what killed Marilyn Monroe, supposedly this and alcohol. Antihistamines: diphenhydramine and hydroxyzine. Helpful sedatives for some, but they are also anticholinergic. I see them as a good placebo. If you’ve got these people and it’s like they’ve got to take a pill. And so you say, “I’ve got some nice hydroxyzine for you. Some Atarax” and you kind of build it up and you say, “We are going to start low. I don’t want to go too high. Don’t use too many of these, tell me if there are any side effects. Okay, here it is. Be careful.” Then it’s like they are taking something really powerful. It’s for those people who just need to take a pill, it’s kind of an acceptable thing. So you might say, “Gosh, you are just telling people to accept the pill and you are not having them work on their issues.” I think that’s a good attitude for like pediatric psychiatry, but I find people 35, 40, 50-years old, if they need to take a pill, you’re not going to change that. So I say, here’s the pill. That’s my practice philosophy. Some would argue with that.
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Beta blockers: good for sympathetic control and people with performance anxiety. Buspirone, a non-benzodiazepine alternative that can take weeks to work. Maybe the drug of choice for patients with drug abuse histories. Now remember, canadian BuSpar is not a panic drug. It’s a GAD, generalized anxiety drug. So question 36: substance abuser comes in, he’s got panic disorder, you probably want to start him on either an SSRI like Zoloft or paroxetine, or imipramine, one of the TCA’s. Question 37: same guy comes in and he’s got generalized anxiety disorder? What are you going to start him on? It’s probably going to be BuSpar, buspirone. There’s going to be a benzo in your choices, and that’s going to be the wrong answer because substance abusers, you don’t want to give them benzos as a general principle. Are they always contraindicated? No. That’s very very controversial, but you know there are some people out there who are medicating their panic attacks with alcohol. You give them benzodiazepine and they will stop drinking and they won’t abuse the benzo. So, it’s a very tough distinction but in my opinion they are not absolutely contraindicated. How about zolpidem? That acts like a partial benzodiazepine. It’s not associated with anticonvulsant activity, it’s not associated with big time benefits. It can cause confusion if the patient is awake while on the drug. Does anyone have any thoughts on zolpidem, Ambien? Ambien works pretty good. The only down side I’ve seen to Ambien is sometimes you will have a kid who will abuse it. He’ll take 20 mg when he is supposed to take 10. Sometimes people have taken 20 with no problem. He’ll take two or three of them during the day and then he’ll ride his bike into trees and be confused and have double vision. It really makes you goofy, so as long as take it and go to sleep, it’s no problem.

Remember, there’s a lot of things that can cause Parkinsonism. There’s medications, there also dementia pugilistica, viral encephalitis, all those things. There’s like a hundred types of things that can cause Parkinson’s symptoms. Now I know that you are all neurologists and you guys are the experts, but I think when I think of Parkinson’s disease I think more of the idiopathic Parkinson’s. And when I think of Parkinsonism I think of this being secondary to something else. So there’s a lot of reasons you can get Parkinsonism, but Parkinson symptoms, to a psychiatrist, that classic cause is neuroleptic. You know, antipsychotic medications.
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Tardive dyskinesia: possibly caused by all the current antipsychotics with zero or very little incidence associated with clozapine and the other atypical agents. What’s the deal with tardive dyskinesia and the newer drugs? That is the sixty-four dollar question. I can say this, clozapine probably has a zero or very small likelihood of causing tardive dyskinesia. If I had to bet money, if I had to take it myself and I didn’t want tardive dyskinesia, probably clozapine would be the drug that I would take. Very, very little incidence and you can almost say zero. How about the newer ones? Well, we’ll get to those later but it’s either zero or close to zero. In any event, it’s much less than with the traditional antipsychotics. Nobody knows what the incidence of TD is. I mean, it could be 2% a year, it could be 80% a year. It’s cumulative, it depends on the study. Nobody really agrees on that. There is no proven treatment for TD. People have tried vitamin E, they’ve tried Clozaril. Nothing really seems to work. Has anybody got any ideas on that? There really is no treatment. Interestingly, it goes away during sleep. You’ll see people with TD, which kind of looks like this. Sort of a mild … that’s what I think of as TD. And then they go to sleep and you don’t see it any more. It’s kind of interesting. It’s also interesting in that it is masked by the drug that causes it. Let’s say you have somebody on Prolixin for 20 years and you take away the Prolixin, suddenly TD may get worse. Why? Because it was not only causing the TD it was masking the TD. Tragically, you’ll have some people with TD of the diaphragm and you’ve got to keep them on that Prolixin or they are not going to be able to breathe.
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This is so classic, this next point. The GI medications look like antipsychotics. Remember I said that earlier? So here’s two classic Board-type questions. Question 13: 18-year-old male comes into the emergency department, sick to his stomach. You give him Compazine. He comes back an hour later with what? Yes, dystonic when you give him Compazine or Benadryl. The other classic one is: you’ve got this 53-year-old diabetic. All of a sudden she is making these lip-smacking motions, these hand motions, what happened to her? Reglan, exactly. Other important side effects: cholestatic jaundice, weight gain, galacturia. You can try treating that with bromocriptine. Dyscrasias and photosensitivity – easy to sunburn.
Typical agents. There’s a lot of typical agents. Let’s talk about the ones I think you need to know about. Chlorpromazine, that’s Thorazine. That’s the potency standard. That thing is older than dirt.

Antipsychotics, used to be called neuroleptics, used to used to be called major tranquilizers a long time ago. General comments: they are traditionally believed to limit dopamine. If you had to pick a neurotransmitter, you’d pick dopamine. That theory is getting shot to hell these days because the newer agents act on all these different receptors, the serotinergic receptors. The tradition was you got too much dopamine, so you are hallucinating or you are delusional. We give you the Haldol, we give you the thorazine, it decreases your dopamine until you are back to relatively normal. That was the old theory. Most are equal in efficacy but different in potency. What’s the difference between potency and efficacy? Quick review. Okay, let’s say that you are walking toward the elevator and you stumble and you break your arm. You’ve got a big piece of your arm bone – let’s say you have a big piece of your radius poking out through your skin – and you say I want some pain medication. And I say, “Okay, here’s some Tylenol.” What are you going to say? “No, I want something stronger.” And I’m going to say, “Okay, here’s extra strength Tylenol.” And you are going to say, “No, I don’t want something more potent. I want something more effective. Something with greater efficacy. I want morphine.” What’s the difference between morphine and Tylenol? It’s not just the potency, how many milligrams it takes, it’s that morphine has an efficacy that Tylenol doesn’t have. It will treat a pain that Tylenol will not. Traditionally, the older antipsychotics were equal in efficacy. Haldol was not better than thorazine, was not better than Mellaril, was not better than Moban, was not better than Stelazine at treating hallucinations or delusions. You prescribed solely on the basis of side effects. That’s the older or traditional antipsychotics. And you could set up a nice little scale. The low potencies had anticholinergic, weight gain, hypotension, sedation. High potency had dystonia, Parkinsonism and acathisia.
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Low potency antipsychotics, very anticholinergic. Remember the anticholinergic mnemonic. Blind as a bat, hot as a furnace, dry as a bone, red as a beet, mad as a hatter. Also constipation, urinary retention, pupillary dilation, and tachycardia. High potency, EPS. Acute dystonia. It’s sort of like this. You have a 20-year-old schizophrenic on your psychiatric unit, he’s out of control, you give him 5 mg of Haldol or 10 mg of Haldol. An hour later he is standing there, his neck is twisted, his eyes are rolled up and his tongue is protruding. What does he have? Acute dystonia. Classically happens in young, muscular males who are neuroleptically naïve. What’s the treatment for that? Benadryl, diphenhydramine or benztropine, Cogentin. Classically. Okay, it’s a few days later. Same guy. He says, “Okay, the Cogentin made me feel better. Now I’m still going to take the Haldol.” And now he’s going like this. He’s standing at the nurses station going like this. He’s got acathisia. He’s got an inner itch to move around. That’s what acathisia is and it can be caused by the neuroleptic medications. People who are paralyzed, who can’t move their limbs, will ask other people to move their limbs for them. That sort of inner itch to be in motion.
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Okay, now it’s four weeks later, he’s still taking the medication. He’s walking around the psychiatric unit like this. What does he have? Parkinsonism. Okay, I’m talking to neurologists, obviously. What do we see with Parkinsonism? The shuffling gate, the cart-wheeling, the masked face, the rolling tremor. To me the tremor is like this. It’s unilateral, kind of looks like this. That’s what I see as the Haldol tremor. Faster or slower than an essential tremor? Slower. I think of an essential tremor as … an essential tremor is going to be a little bit quicker, I think. More like that. Contrast that with a lithium tremor. When I see a lithium tremor I think of it as kind of a fine … I had three pots of coffee just now, sort of a fine tremor. That to me is sort of the classic Parkinsonian neuroleptic medication.

Other antidepressants: venlafaxine, that’s canadian Effexor. It works on serotonin and/or epinephrine. Relatively smaller risk of drug interactions than with some other agents. Also good for geriatric patients, in my opinion. There’s an XR form now. There is risk of elevated blood pressure. That’s maybe your one Board question, if I thought there was going to be one, is that it can – in some people – increase blood pressure. But I don’t think that’s at all a major impediment to prescribing it. Bupropion: may involve dopamine as a mechanism of action. But it’s still unclear. Low on the sexual side effects. The people who advertise it really beat that drum hard you know, and say, “Look, we don’t have the sexual side effects the other drugs do.” Possibly – this is controversial – but possibly lower induction of mania for bipolar patients. Put a check mark by there and put this, if they say, “Look, I’ve got somebody with bipolar disorder and I’m afraid to give them an antidepressant because it might send them off into mania – they are bipolar depressed right now, they are in the depressed phase – what drug do I give them?” a lot of people, the first line is Wellbutrin or bupropion. Really the ideal is lithium. Lithium is a true mood stabilizer. If you are up it brings you down, if you are down it brings you up. But it’s not a great antidepressant. It’s a mild to moderate antidepressant but it’s not a wonderful antidepressant. So most people with bipolar disorder cannot get by with lithium alone. They need lithium, for example, and another antidepressant added on to that. Your first line choice is commonly Wellbutrin, or bupropion. May cause seizure risk in bulimic patients or epileptics, important to know.
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Nefazodone, or Serzone: low sexual side effects. It can raise levels of alprazolam or triazolam, that’s Xanax and Halcion. I would put a check mark by the next one because that could be a legitimate Board question, contraindicated with these three drugs, terfenadine, astemizole and cisapride. I think that’s Seldane, Hismanal, and I think Propulsid. Trazodone, used more as a sleep agent in recent years because of sedating side effects. You know a lot of times you use trazodone at night can cause hypotension, can cause priapism. That can show up on Boards. Mirtazapine is Remeron. Pretty new. I don’t think it’s classic enough that you could see Board questions about it but, you never know. May cause weight gain, rare cases of blood problems, dyscrasia’s.