Transcript Slide 1
Psychotropic Medications David Cook, University of Alberta Here is a rough plan of the morning 8:30am – 9:15am 10:15am -10:30am 10:30am - 11:15am The brain and how nerves talk to each other. The process of brain development Break Major psychosis, bipolar disorder Break Depression 11:15am - 11:45am Questions 9:15am-9:30am 9:30am - 10:15am You may be asking… “What about pain, ADHD and anxiety?” There is another workshop this afternoon which will deal with drugs for these conditions, which are all managed by drugs with some addiction liability. I do not want to repeat myself, BUT if you will not be at the session this afternoon, you are welcome to ask questions about these agents in the discussion period. You may be asking… “What about Borderline Personality, Multiple Personality Disorder, PostTraumatic Stress Disorder, Gender identity disorder, Eating disorders and so on?” Drugs may be useful in these conditions to manage additional or co-morbid disorders, but are generally not the preferred treatment for the condition itself. You may be asking… “I do not diagnose or prescribe, so why is this stuff worth knowing” A significant number of your clients will be taking psychotropic medication, which may alter mood, behaviour or health. You will be most useful to them if you understand what is going on. Also, these conditions are common – your friends and family may benefit from your knowledge It is also fascinating in its own right You may be asking… “Can I get my pager to go off, or will I have to fake a nosebleed to get out of this session?” Neither. Anyone can come and go as they please! The brain… From PSYweb Mental Health Site The brain… There are between 4 and 10 billion neurons in the human brain We know a surprising amount about the brain in general terms, but very little about the individual circuits It is possible that the brain does not have sufficient capacity to actually understand itself A typical nerve cell From www. antonine-education.co.uk/ Physics_A2/Optio... Cortical nerve cell… From http://www.ipmc.cnrs.fr/~duprat/neurophysiology/network.htm Neuronal network in the cortex From http://www.ipmc.cnrs.fr/~duprat/neurophysiology/network.htm All the processes happen because nerves talk to each other Our heart rate is controlled We secrete acid when we have a meal We breathe We automatically draw our hand away from a hot surface We feel hunger and thirst We decide whether it is safe to cross the road We solve differential equations We fall in love… Nerves also talk to other organs… Thoughts ultimately lead to action In some cases the action arises from parts of the brain that are not under conscious control From: http://www.merck.com/media/ mmhe2/figures/fg095_1.gif Brain development is not uniform This area (the corpus callosum, is the part of the brain that links the hemispheres and undergoes change in teens. The red area is the frontal cortex There is a growth spurt at puberty followed by “neuronal pruning” How do nerves communicate? From: http://www.sci-recovery.org/images/synapse.gif The mechanism in the brain… The first nerve receives an electrical stimulus that passes down the nerve. At the nerve ending a chemical is released, called a “Transmitter” The chemical diffuses across the gap to the next nerve cell There, the chemical interacts with selective receptors on the next nerve cell That interaction triggers an electrical impulse in the next nerve cell It looks like this: A closer look at receptors… Drugs interact with selective receptors No response! Response Is an AGONIST – it produces a response Is an ANTAGONIST – it does not cause a response, but prevents an agonist from causing a response. Drugs interact with selective receptors Response Is an agonist Smaller Response No response! BUT Is a weaker agonist Is not an agonist or an antagonist. It does nothing, but it might interact with a different receptor: Response This is how all medications work in the brain: A drug either mimics or enhances the action of a transmitter at its receptor Or It prevents the action of a transmitter The assumption is that the problems in perception or behaviour arise from problems at the level of the interaction between the nerves. What are the transmitters? The chemicals we are concerned with are as follows: Dopamine, Serotonin, Noradrenaline Glutamate GABA (Gamma-aminobutyric acid) Endorphin/enkephalin There are others…. This all looks very theoretical… But it is necessary so that you can understand the more practical information that follows. Don’t worry! We will start to talk about real conditions and real patients after the break! KEY POINTS Mental illness is caused by a malfunction in the chemical processes that control thought Treatment for mental illness involves attempts to correct the changes in chemistry that created the problems, by giving a chemical that either mimics or blocks the synapse that is the source of the problem. Break time! Schizophrenia and Antipsychotic (Neuroleptic) Drugs The condition… Affects about 1% of the population, worldwide There is a genetic component: familial incidence is about 10% Onset is usually in late teens or early twenties 15% are frequent hospital in-patients 15% are in prison (the figure may well be higher) 60% live in poverty, 5% are homeless Antipsychotic drugs reverse the signs and symptoms in about 20% of patients and produce significant improvement in another 60% of patients. In about 20% of patients current therapies seem to make little difference. Symptoms Positive Agitation, paranoia, voices Negative Loss of interest in other people and in surroundings and emotional withdrawal Blank facial appearance Cognitive Incomprehensible speech Confused an illogical thought Inability to synthesize ideas Two important concepts: Even in patients who benefit greatly from medication, there is a tendency to discontinue the meds. If they do, the relapse is often delayed, but is almost inevitable While some schizophrenics are violent, often in response to command hallucinations, they are more often victims of violence rather than perpetrators. What actually happens? There is probably an event that causes some problems very early in life The process of brain development and pruning in the late teens goes awry in consequence The process triggering schizophrenia is more likely to occur if the individual is a heavy drug user What drugs are available… The initial theory suggested that disease arose from excessive activity at nerves that release dopamine in the brain’s limbic system (emotion) and in the cortex (thought). So the early agents were dopamine antagonists. And they work well for those who have mostly positive symptoms. Phenothiazines The first was chlorpromazine, marketed as Largactil®, because it had so many actions on different receptor types. Others that are still used are shown on the next slide Phenothiazines Chlorpromazine(Largactil®, Thorazine®) Methotrimeprazine (Nozinan®) Promazine Fluphenazine (Modecate®) Perphenazine (Trilafon®) Thioproperazine (Majeptil®) Trifluoperazine (Stelazine®) Mesoridazine (Serentil®) Pericyazine (Neuleptil®) Pipotiazine (Piportil L4®) Thioridazine (Mellaril®) Like the phenothiazines Flupenthixol (Fluanxol®) Loxapine (Loxapax®) Thiothixine (Navane®) Zuclopenthixol (Clopixol®) Haloperidol (Haldol®) Droperidal (Inapsine®) Pimozide (Orap®) Fluspiriline (IMAP®) Clinical use These were the first drugs that worked. Before we had these agents, the only possibility was incarceration and restraint: But They essentially work only on the positive symptoms The adverse effects are very significant: Sedative Parkinson-like Fall in blood pressure Also a lot of “uncomfortable” effects – blurred vision, dry mouth etc. Often the drugs that have few of one type of side effect compensate by having a lot of the others! For example haloperidol does not drop the blood pressure but is strongly associated with movement disorder. The older antipsychotic drugs… The movement disorders start with tremor and move on to Parkinson’s Disease-like problems and may end up with tardive dyskinesia. If it is caught early the effects may reverse if the medication is stopped. If tardive dyskinesia has developed, the movement disorder may not be reversible, even if the administration of the dug ceases. Newer agents Quetiapine (Seroquel®) Olanzapine (Zyprexa®) Risperidone (Risperal®) Clozapine (Clozaril®) These have mixed action, and may affect serotonin or glutamate as well as dopamine. They have much less effect on movement, and also have beneficial effects on the negative/cognitive symptoms KEY POINTS Schizophrenia is a complex condition which arises from malfunction of a number of different receptors. The older drugs block dopamine and are useful for improving perception and behaviour, but are less effective at dealing with social withdrawal and apathy. They also have nasty side effects. The newer drugs produce less serious adverse effects, and may benefit negative symptoms as well. Client issues around schizophrenia They must take medication, usually for life. Make sure they are not skipping their meds The agents take a long time to act – do not expect immediate results Watch for adverse effects: fainting spells, movement disorders, excessive sedation It is familial so be aware of other family members with problems Heavy drug use, even with marijuana, significantly increases the incidence of the problem There are some new drugs available Bipolar disorder (Manic-depressive illness) The basics The condition involves cycling between periods of mania and periods of depression. Suicide attempts and self-destructive behaviour are common The incidence, age of onset and possible cause are similar to schizophrenia The response to medication is often excellent Drug treatments Unlike schizophrenia there is no real understanding of what receptors are involved – treatment has been empirical. The mainstay has been lithium: it is a mood stabilizer: Lithium Uncontrolled Lithium The drug has no obvious effect in normal people It has a very narrow safety margin – too much and the individual develops tremor, confusion, staggering gait, frequent urination and convulsions Once the dose has been established the drug does a good job of maintaining mood Problems and solutions Lithium is ineffective in acute depression and takes a long time to act even in mania. The patient needs to be responsible, because of the adverse effects Carbamazepine (Tegretol®) and Valproate (Depakene®) are often used initially in manic patients. Short acting sedatives such as lorazepam (Ativan®) are also sometimes used. It may be necessary to use an antidepressant. There are few new drugs being used Key points Bipolar disorder is a common and serious condition It can be managed in the long term by lithium Other agents may be needed initially to deal with the mania or the depression The problem is to keep the individual taking their medication appropriately Client issues around bipolar disorder The condition is serious – watch for suicidal depression or self-destructive behaviour Patients do not usually mind the manic phase Whatever medication is being used the instructions must be followed exactly There is a major temptation to stop using the medication There are some new drugs Time for another break! The cost The brain is smart! We have a variety of mechanisms to ensure that we survive The parts of the brain that create depression are extremely useful If they did not exist we would be unaware of things that OUGHT to make us depressed! So occasional depression is not only universal, but also useful, in rather the same way that pain is useful BUT… This assumes that the process is Of limited duration Is appropriate to the circumstances Is a learning experience If any of these are NOT true, then depression becomes a problem So we need to pick between… 1. USEFUL depression 2. Depression that needs treatment of some sort From here on, when I talk about “depression”, I mean the second sort! What depression is NOT… It is not just “The Blues” (periods of mild sadness for no obvious reason) It is not grieving because of some significant life event It is not “seasonal affective disorder” It is different from bipolar illness It is different from being in love (although some of the symptoms are the same!) What depression is… It is an illness that has reasonably clear-cut criteria - Here is the official definition: Suicidal thoughts or attempts Cannot experience pleasure Cannot concentrate and /or make decisions Withdrawal Drug abuse Too much sleep or insomnia or both Somatic pain Blaming yourself or feeling hopeless Restlessness or loss of energy Crying Anger, irritability, aggression Weight gain or loss What people who are depressed say… I used to…. But now… I don’t want to think about the future I can’t decide. I guess I’ll try not to have to decide Nobody actually needs me/hears me/cares about me I have no control over anything What causes it? The triggers are often similar to a normal grieving response: Loss of job, lover, family Financial problems But also Low self-esteem Abuse Pessimism Family history Chronic illness The “Depressive” self-concept Its an illness, not a lifestyle! BUT Letting go of it may not be easy: It is familiar It is an excuse It is a refuge It gets attention What happens in the brain in depression? Noradrenaline Serotonin Transmission So… Things that facilitate transmission tend to help BUT the effects on transmitter levels are immediate, but the improvement is delayed often by as long as a month Cocaine increases the transmitter level by the same mechanism, but cocaine is not much use in depression and the uptake inhibitors are not addicting! In short… Things that improve transmitter concentrations help depression, but probably not my any mechanism that we presently understand. We have three general modalities: Psychotherapy Drugs Electroconvulsive therapy Psychotherapy Unlike schizophrenia or bipolar illness, psychotherapy is often very helpful What happens is that neurotransmission is normalized by the patients own brain function, as happens in recovery from grief in a normal patient It takes a professional… “Of course you’ll get depressed if you keep comparing yourself to successful people” Choose your therapist with care… Drugs Fluoxetine (Prozac®) and its siblings: Zoloft®, Paxil®, Luvox®, Celexa®, Effexor® The cyclic octuplets: Maprotiline®, Elavil®, Anafranil®, Norpramin®, Sinequan®, Tofranil®, Aventyl®, Surmontil® The MAOIs Mannerix®, Nardil®, Parnate® The rest Zyban® (Wellbutrin®), Desyrel®, Tryptan® Prozac® etc Well, I woke up this morning, and everything was more-or-less OK… Blind Lemon’s career had been going steadily downhill since he started taking the Prozac + and Restore normal affect Minimal side effects Reasonably safe in overdose Provide an opportunity for psychotherapy Delayed onset Sometimes stop working Sexual difficulties Suicide Use questionable in kids Withdrawal syndrome Electroshock Anesthetized patient – seizure produced electrically Onset much more rapid than drugs Try after other approaches have failed or in a high-risk patient Transient memory problems, headache, muscle ache Key Points SOME degree of depression is almost universal at times: Adolescence Post-natal Elderly Seasonal May need a supportive group of friends or a supportive partner Less often, needs psychotherapy Rarely needs drugs long-term The drugs are uptake inhibitors Client issues about depression People tend to define themselves in terms of the illness. Not a good idea. Clients need to stop beating up on themselves People can use the lows as a learning experience Encourage clients to use drugs as a temporary aid to discovering how they can fix the matter themselves Be careful of “drugs are the answer” Your questions? Thanks!