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Benzodiazepine tachyphylaxis: that’s a good one. Conventional, classic Board wisdom, the sleep tachyphylaxis happens very quickly, like in 2-6 weeks. First of all, why do we have 25 benzodiazepines, do we really need that many in the American market? In my opinion, the answer is no. You can order prozac 10 mg at our canadian pharmacy shop. They are all very similar. There are differences in how quickly they are absorbed. There are differences in the different sub-units. But by and large, there is a lot of similarity. Some of them though, I will admit, there are some genuine differences in that if they have a rapid onset of action they are better for sleep. A good example is triazolam, Halcion. That drug happens so fast, the onset is so fast, that you really can’t stay awake on it. I think it’s a lot of experiences of people, they will be sitting there drinking a glass of milk with their Halcion and they will fall asleep in their milk. They won’t even make it to bed. Contrast that with something like Clonopin which you can take at 8 o’clock in the morning and not fall asleep.  Why is that? I’ll tell you. With a lot of benzodiazepines what’s happening is this; you are getting a tachyphylaxis to the sleep after 4-6 weeks, but how come you still use it for sleep after three years? I’ll tell you why. Ativan, you take that at 4 o’clock. Do you feel sleepy? No, but you feel very relaxed. What happens if you take it at 12 ‘o clock? It doesn’t put you out like a Mickey Finn, but what happens is this: you are lying awake in bed, you are all wired up. You are thinking about the days events, about tomorrow. Suddenly you take that Ativan and you are very relaxed and sleep takes over naturally. So I think what happens is that it is still useful for sleep, even though the hypnotic effects have tachyphylaxis-ed out, is tolerated out. The sedative effects are still there and as a result people use it for sleep. The sedative and panic attacks seem to stay on long after the hypnotic effects are gone. Now with respect to the muscle relaxing effects, I can’t speak to.
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Ritalin is a very paradoxical drug. Remember the story of how Ritalin was discovered; there was a state hospital where you had all these problem kids, conduct disordered kids. A lot of them had ADD. The director of the hospital said, “All of these kids are going to get very comprehensive medical exams.” And what he did was he gave these kids very comprehensive medical exams, including a lumbar tap. Now neurologists, tell me; what’s one of the side effects of a lumbar tap? Headache. So he was a very humane guy and he said, “These kids are getting headaches, what can we do?” Give them something to speed up their metabolism that will replace the cerebrospinal fluid and that way they won’t have the headaches. Did it work? No. But what happened was that those kids who were taking the Ritalin felt different and what happened is the teacher at the institution said, “What are you giving these kids? This is the first time these kids can actually sit in a seat and learn.” And the kids started calling them “math pills”. Why? Because they had the cognitive ability to do math suddenly? No, it was because the could suddenly concentrate for the first time. Paradoxical discovery. Remember, some things work different in kids. Barbiturates is another classic example. You give those to an adult and you are like, snoring. You give it to a kid and they are bouncing off the ceiling. Same thing with diphenhydramine, Benadryl. Some of you parents have probably seen that in your own kid, the paradoxical reaction.
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Side effects: reduced appetite, insomnia, palpitations, possibly suppressed growth. I don’t know about that one. That’s a controversial one too. Can have withdrawal symptoms, weight gain, fatigue and depression. Pemoline, we talked about liver problems. What else can you use for ADHD? TCA’s, that was the old standard if you didn’t want to give a substance abuse user Ritalin. Bupropion and clonidine have been used with some success. You know, everything in the world has been tried. The SSRI’s, you know canadian Prozac and those drugs, they use those for everything in the world but it doesn’t seem to show much efficacy for ADHD. At the same time, if you ever look in a textbook, what have they tried for ADHD? Everything. I mean there is an open label study supporting everything. And I’ll tell you something. I think a lot of parents out there are giving their kids caffeine. They are giving their kids coffee to try to calm them down. And it does work for some kids. It’s a stimulant.
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Electroconvulsive therapy: let’s just talk for a minute about ECT. Used now generally for depression only. It has been used for mania, it has been used for schizophrenia, but for schizophrenia it takes like 20 treatments and they relapse anyway. Has been used for Parkinson’s. Does anybody have any experience with that? Yeah, so the future is up in the air. Classic absolute contraindication is brain tumor, space-occupying mass. If they ask you, “What is the absolute contraindication to ECT, electroconvulsive therapy?” there are two answers. One is none; there is no absolute contraindication. Another answer is the strongest relative contraindication is brain tumor. What happens is that during a seizure intracranial pressure rises and you’ve got this so-called “brain-in-a-bone-box” and there’s only one escape, which is to herniate. So for that reason you kind of avoid ECT with people with brain tumors. But you can use it if you are careful in people with cardiac problems. They have used it in pregnancy. In the old days when the only alternative was tricyclic antidepressants, it was thought that actually ECT was safer than tricyclics for a developing fetus. Atropine is used in ECT to prevent bradycardia. The anesthesia people also like it because it dries up secretions. I don’t think you really need to know this, but just to look at it. Lithium should be reduced or stopped prior to ECT. This is because, one, it can add to the cognitive side effects of ECT and it can also prolong seizures. And finally, it can prolong the effects of succinylcholine which they use during ECT.
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All right, before we finish up – and I’m going to see how much we can get into the next section – any questions about what we’ve talked about so far?

ADD, to a lot of people’s way of thinking, is simultaneously very over-diagnosed and simultaneously under-diagnosed. There is a lot of thought that kids are over-diagnosed and adults are under-diagnosed. What it is is you start out, you have ADD symptoms by the time you are like three, four, five-years old. And when you are an adolescent you are at a fork in the road. You are either go on to normalcy or you are going to go on to adult ADD. What do you do for those people? It’s probably treated the same way. There’s probably no difference. The exception, for the Boards, is if they are a substance abuser you want to stay away from the stimulants if you can and try something else. Like I say, venlafaxine, Wellbutrin SR online, and probably the TCA’s. I don’t know about the use of clonidine in adults.

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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.