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hello, i'm geraldine moses. welcome to the program, psychotropicdrugs: what's safe and what's not. we've come a long way since the 1940s, when psychotropic drugs revolutionisedthe care of the mentally ill. they've virtually becomefirst-line treatment of mood and behavioural disorders, and in recent years there's been a waveof new psychotropic drugs developed. but being new, we need to be aware of the safety issuesthat are associated with their use.

and the risk of medication misadventureis often higher with psychotropic drugs. our program looks at antidepressants,mood stabilisers, anxiolytics, hypnotics and antipsychotic drugs. we'll examine issues related totheir toxicity, interactions, overdose and monitoring for adverse effects. we'll also consider the useof psychotropic drugs for special populations such as children, pregnant womenand the elderly. we're coming to you across australia

through the rural health educationfoundation's satellite network. there are a number of useful resourcesavailable on the rural health educationfoundation's website, which is: now, let's meet our panel. dr anthony harris is a senior lecturer in the disciplineof psychological medicine at the university of sydney,and a consultant psychiatrist for the prevention, early interventionand recovery service. - welcome, anthony.- good evening.

christine culhane is a pharmacist with20 years' experience in mental health, including specialist roles in psychiatric inpatientand outpatient settings. she currently managesthe psychotropic drug advisory service on the telephone in victoria. - welcome, christine.- hi, geraldine. chris alderman isthe director of pharmacy at the repatriation general hospitalin south australia. he's also associate professorof pharmacy practice

at the university of south australia. - welcome, chris.- hi, geraldine. dr jonathan isles is a generalpractitioner with 19 years' experience initially in solo practice, then for the past nine years,in a group practice in suburban hobart. he has an interest in geriatric medicineand sports medicine. - welcome, jonathan.- good evening, geraldine. to begin this important show, let's have a brief overviewof what psychotropic drugs are.

is there a definition,and what are the safety issues? chris, could we start with you? is there a definitionfor what psychotropic drugs are? there are lots of definitions,and you read different ones. but the one i thought best describeswhat psychotropic drugs are, are the drugs we use with the intentof influencing thoughts and emotions. that's a definition that allows usto think of some drugs that under certain circumstances, wouldn't be regarded aspsychotropic drugs,

in a different context can be regardedas psychotropic drugs. for example, analgesics? analgesics can havepsychotropic effects, but i'm thinking more along the lines ofmood stabilisers, anticonvulsants, for example, that we use for differenttherapeutic applications elsewhere. what do you think of issuesdeveloping in this area, in terms of safety? what we've seen, since the early 1990s,

is an absolute explosion inthe availability of psychotropic drugs. there's so many more different agentsavailable. we're still on a learning curveabout these medicines. we're still understanding an evolvingpicture of their safety profile, how to use them best,how to use them in combinations, and to be aware of the interactionsand the problems we only see when these drugs are used in a large-scalepost-marketing surveillance phase. that's really somethingwe're all still coming to grips with.

anthony, if you could comment on this. we're saying,what's safe and what's not. amongst your colleagues, do you havethese discussions about safety? certainly, and the huge increase in thenumber of drugs is one of the problems. the tendency to mix and match,to combine too many drugs together, is a problem in this field,let alone the individual side effects. surely also the fact that clinicaltrials usually are for a short period, yet in many patients, we're using themfor a very extended period. these are drugs treating illnesses whichare often long-term for the patient.

the trials are often narrow, and the populationsin which they're done are quite unrepresentative sometimesof the clinical populations we treat. one of the issues we're dealing withis the lack of evidence. we're often flyingby the seat of our pants. we can go back to chris and talk generally about one groupof drugs, say antidepressants. when we look at those, how do we choosebetween then as pharmacologists, or people interested in pharmacology,in terms of what's safe and what's not?

there are general ruleswe can apply and think of when choosing antidepressantsfor an individual patient. we know that major depressive illnesses, and many of the other illnesseswe use antidepressants for are chronic relapsing illnesses. we know that medicationsthat worked last time are probably not a bad choicefor this occasion if everything else is equal. that's one issue we take on board.

we think about other medical conditionsthe patient might be affected by, the medicines they might be takingat that time. we think about things like suicide risk,cost and convenience to the patient. it's ideal if we can get a drug that canbe taken one dose, once a day. it's a major advantage for our patients, because no medicine can workunless it's being taken. one issue that's affecting the useof antidepressants is that new ones are coming outall the time, yet we're still using some other onesthat came out in the 1940s and 1950s.

do you see safety issuesin using the older drugs? all of the drugshave their own safety issues. it's important for usinvolved in using them to be aware of what they are,make ourselves familiar, and to accommodate thatin the way we use the drugs and to monitor patients in such a wayto allow us to be aware of issues as they arrive, and to address themproactively with the patient. making the patient their own advocate,of course, is another important strategy that we can employ so that people canadvocate on their own behalf,

in interactions withthe health professions. generally, jonathan, are there issueswith antidepressants in your practice that you see coming up all the time? sure.well, i don't want to say my practice. but one of the things that i fear is that gps, over the time that thesenew agents have become available, have got the feeling thatthese are so much more safe than their older cousinsor parent drugs. - like monoamine oxidase inhibitors?- exactly.

which now, maybe for some young gps,they've not been experienced enough to know whatthe old monoamine oxidase inhibitors do and what side effects they have. nonetheless, even the newer ssris,the thing that i fear is that we tend to use themin a set-and-forget mentality a lot. ensuring the right diagnosisis one thing, and making sure we have linksto specialist colleagues is important, but i fear that sometimeswe use these drugs because they're new, and because we get the feeling thatthey must be safer if they're newer,

and that they must be more effectiveif they're newer. they're thingsthat we can get concerned about. we're now going to talk aboutsome special populations, so we'll move to our first case study. this case is jane.she's a 35-year-old woman. she was diagnosed withpostnatal depression following the birth of her daughterthree years ago. back then,she was prescribed fluoxetine, which was stoppedafter a year of treatment.

but jane is pregnant again. she's now in her first trimester, and concerned about takingantidepressants during pregnancy and thinking about taking st john's wortinstead of a prescription drug. this is a not uncommon scenario. i wonder if we can talk to christine about the sorts of questions you geton your drug-advisory line about drugs in pregnancy. give us some guidance on what's safeand what's not.

jane is probably fairly typicalof people who ring up. people ring up and want to know, is itok to take this drug in pregnancy? sometimes they're pregnant already,so it's a knee-jerk reaction - i'm pregnant, i'm taking drug x,what do i do now? other times it's,i'm planning to become pregnant, and i have a history of thisor i am taking this. how safe will that be? what if i become sick?can i take this medication safely? what's it going to do?

somewhere in the scheme of things,they need to not lose track of, where am i in terms of my illnessin this process? if you're not actively unwellat that point in time, you just need to put in safeguardsalong the way to make sure that you stay welland that it's monitored. for this patient, which would bethe class of antidepressants which would be considered safestduring pregnancy? jane has responded to fluoxetinein the past. ssris are generally fairly safein pregnancy.

i probably wouldn't advocatest john's wort, and i probably wouldn't advocateanything to be taken in a preventative waywhen she's not actively depressed. is it also because oflack of safety data with st john's wort? there's very limited informationwith st john's wort. there is nothing to suggestit's a problem. there's nothing to suggest it's safe. - often the case in pregnancy.- with all of our medications. so we fly by the seat of our pantsa lot of the time

knowing that we've gotvery limited information to work from. you tend to know very quicklywhen something goes wrong, not so quickly when things go right. we do know that ssris in generalare fairly safe. given that she's used fluoxetine,you would give it serious consideration. the downside up-front would be thatit hangs around for a long time. so if something goes wrong,you can't get rid of it in a hurry, and you've got the risk of accumulationin the foetus. what about when she gets closeto delivery and...

it's not just that. it's also that fluoxetine,because it hangs around longer, tends to cross the placenta at a slightly higher ratethan the other ssris. there is the risk of increased exposureas well. can you also comment onthe recent safety data on paroxetine? some people suggestedthat it's teratogenic. there's evidence to suggestthat there's an increased risk of cardiac septal defectswith paroxetine.

there certainly is an increaseover the normal rate in the community. that risk is relatively low, but the safety data wouldneed to be weighed up against the person's need at that time. it's not enough to say, don't use it,because that's not always right. you need to weigh it up against themother's relative risks at that point. doing nothing when someone isseriously depressed during pregnancy also carries its own dangers. which we knowin all sorts of conditions.

chris, i believe you wanted to makea comment about the antiplatelet effect that ssris have in pregnancy,and the safety issues there. it's a wider issue, but certainlythese are drugs that are known, in some cases,to interfere with platelet aggregation. there's widescalepharmacoepidemiological data now evolving to tell us that theyincrease the likelihood of bleeding in all kinds of circumstances. if you look at the fine printin the product information, you'll find references to things likeepistaxis and menorrhagia

and bleeding haemorrhoidsand purpuric rash and you can go on. some people hold concerns about the useof ssris late in the third trimester because they believe it could contributeto increased perinatal complications related to bleeding. are you suggesting thatthey come off the antidepressant? i don't think that's a call you can makein a general sense. that's something you need to think aboutwith each woman and each child-to-be. it's a case-by-case analysis. depending on how sick that lady isat that time,

that would guide our thoughts. bearing in mind also,if we're not talking about fluoxetine, perhaps when we're talking aboutanother ssri, the last thing we want is complicatingthe parturition with discontinuation syndrome. - jonathan, you're rigorously nodding.- i'm itching to say something. this lady is very interesting. there's lots of scenariosthat could be the real case, insofar as she may be already taking stjohn's wort and she's fallen pregnant.

will she tell you? will she not?is she too embarrassed to say? let's assumethat's a big issue in itself. but the major issue,from a general-practice point of view, is that we see these sorts of peoplecoming along a lot. they need a lot of reassurance thatwhat did happen previously isn't necessarily going to happen,or if it is, that we'll monitor it, and that we'll know what to doat the right time. as you say, with fluoxetine,one of the things i'm keen on is for each person to have their favouritemedication in each particular class.

it may be that a gp says, 'i don't usefluoxetine. i use something different.' it's important to know whatthe different ssris do in pregnancy. the shorter-acting onesmay be of benefit in terms of getting people who becomedepressed during a short period undepressed a lot quickerthan fluoxetine might, which sometimes has a long durationof action. i'd like to raise the issue,and anthony, if you want to comment. i wanted to say, what if this patient isnot just depressed, but she's bipolar? then we have to look at

perhaps using lithiumor mood stabilisers in pregnancy. to comment on the discussion earlier, this comes back toa risk-benefit analysis, which will be your themefor the evening. starting somebody on any medicationduring their first trimester when there's no clear indication issomething i think we'd all avoid. one needs to keep into accountthe severity of depression that the lady experiences. if it was a mild depression before,she has no symptoms at the moment,

it's quite clearthat we'd be looking at supportive work, perhaps cognitive behavioural therapyas delivery dates come close. but if this lady had severe depressionor in fact perhaps had bipolar disorder, we'd be thinking aboutthat risk-and-benefit analysis. coming back to your question about if this lady happened to havebipolar disorder, perhaps starting on a mood stabiliserif she'd had a history of relapse or of severe illness immediatelyafter delivery is a real possibility. but this family of drugs don't look nicein pregnancy.

no, it doesn't. one would think about using lithiumnot during the first trimester but later on in the pregnancy, keeping in mind the difficultiesthat might occur during delivery, and thinking about the rapidfluid shifts, and lithium being a salt, which can be a complicating factor. how frequently do you do lithium levelsduring pregnancy? more frequently than one normally does. once a month? once a week?

as the date becomes closer, yes,an increasing frequency. you were saying earlier that lithium is not as big a problemin pregnancy as we used to think, in terms of being a teratogen? yes, i think that's true. the more recent information suggeststhat the risk is going away from lithium and is perhaps much more an issue,in terms of teratogenic effects, with mood stabilisers, which have beenused more widely in recent years. do you mean sodium valproate?

sodium valproate in particular, which has become a very commonly usedmood stabiliser, is now recognised as havingquite significant teratogenic effects. is carbamazepine being used much asa mood stabiliser for bipolar disorder? no, it's falling out of favour. lamotrigine and some of the otherantiepileptic drugs are being used. certainly lamotrigine isbeing established as an important mood stabiliser. we're unaware of any antifolate effects

or spina bifida associationwith lamotrigine? as far as i'm aware there's very littledata about the birth of children. geraldine: it's hard, isn't it? anthony: even from women with epilepsy. we have no spare people to practise on. it's so hard to know what the safety is. one of the interesting things i've heardis that things change. once again, the old adage is thatold information is old information. you need to keep up.

the paroxetine issue is now obvious. the lithium thing that we all said,stay away from, may not be so harsh. in the future, these ssris maybecome much more mainstream. great point. thank you, jonathan. information changes so quickly,particularly in this area. perhaps we'll move on to our next case,which is sort of jane grown up. we now have a 60-year-old womanwhose name is anne. she used to have bipolar disorder. she was taking lithium for 25 yearsbut was ceased off that two years ago.

we don't know why. she's been fine since,but lately she's been tired, depressed and has had trouble sleeping. she now presents to her gp to askwhether she requires an antidepressant. jonathan, i wonder howyou would approach this woman with a history of bipolar disorder. aren't a lot of antidepressantsassociated with triggering manic episodes? well, exactly.once again, that's what we understand.

the issue with anne grown up is that we have some symptomsthat could be some other things. if she presented general practice, deciding she was depressedis maybe what we'd come to, but prior to that we would rule outa lot of reversible causes. the fact that she stopped her lithiumtwo years ago could possibly be thatshe has some resultant effects of that. she could be hypothyroid in this case,for example. so reversible causesare really important.

but after that, if i'm coming tomy diagnosis of depression, i'm coming to that stage wherei have to say, 'what happensif i put her on an antidepressant that might stimulate a manic episode?' i'm not confident enoughto just bung her back on lithium, even though chris mentioned that oftenthings that worked before work again. patients have told mefrom their psychiatrists in the past that if you come off lithiumhaving been on it, it might not work well the next time.

at this stage,i'm going to ring my colleague, who happens to be sitting doing nothingdown the road. anthony: and there's a slot available.extraordinary. what your patients have been telling youis not completely correct, but certainly, there is strong evidencethat particularly the tricyclics can trigger a manic episode if startedin the absence of a mood stabiliser. the evidence is far less strongfor ssris about that. i think if this lady has had a historyof responding to lithium in the past and the pattern of illness would suggest

that the mood stabiliser lithiumhas helped her, the first port of call would perhaps beto start her back on lithium. lithium has a mildantidepressant effect. we may be seeing the beginningof another cycle of mood instability, so that would be a very safe way ofbeginning an antidepressant treatment. also, if added antidepressant therapywas required, you'd be much more confident aboutintroducing an antidepressant later on with a mood stabiliser on board. thank you very much for that.and i ask you back,

what about one of thesemore modern mood stabilisers that has an antidepressant action,like olanzapine? should i put her on that instead? it becomes a matter ofrisk and benefits, and something foryour individual patient. the newer mood stabilisers,the antipsychotics - olanzapine or quetiapine, both of which have been approvedfor use in bipolar disorder, they have their own runof significant side effects.

if lithium has treated this lady well inthe past and she's familiar with them, i would suggest that that would bethe first port of call. i propose that this lady, anne, not onlyis suffering from symptoms of depression but also anxiety. sometimes we see in practice antipsychotics like olanzapinebeing used to treat anxiety. what is the evidence to support that? it's not huge, for anxiety. as you know, olanzapine is onlyindicated for psychosis

in bipolar disorder at presentin australia. but it has been used over a very broadrange of psychotomimesis, as the first generation antipsychoticswere 20 or 30 years ago. - like largactil.- yes. stelazine was used in many,many different patients, as was thioridazine/mellaril. this is true across the boardfor psychotropic medications - they tend to jump category. antidepressants are certainly not usedjust as antidepressants.

so for this lady, i think the balanceof side effects would suggest that using an ssri would be less likely to cause some of the problemsof weight gain, which are commonly a problemwith some antipsychotics, or the undue sedation,which might be a problem for anne. what we often seein this sort of patient is that she'll end up on polypharmacy. as time goes on, she may even be onan antidepressant and a mood stabiliser and an antipsychotic.

would you like to comment on the prescribing of multiplepsychiatric medicines? then i'd like to ask christine to talkabout drug and directions. polypharmacy is a real issue. the temptation with so manyof these patients is when something hasn't worked,to add something else on top in case that will push along the processa little bit. the more sensible clinical courseis to say, that hasn't worked. i will now stop it,

ceasing it slowly, not wantingto stop something too rapidly, then trial a different medicationwhich has some evidence behind its use. rather than add more medications oneach time, it's importantto take stock of the situation. i would suggest stopping a medicationbefore starting another. keeping it simpleand avoiding polypharmacy. before we move onto drug and directions, we've had a question from a pharmacistin north queensland, marisa pilla, who asked about the switchingof antipsychotics from one to the other

and the difficultyin knowing how to do that. do you have guidance on how to switchfrom one antipsychotic to another? most antipsychoticscan be switched over, one being tailed off when the next oneis being slowly started. it depends a little upon how acutelyunwell the individual patient is. if they're very psychotic,that process is going to be quicker than what you might otherwise do. the difficulties really occurin a number of situations, one in which you switch from a high doseof antipsychotics

and then you choose a relatively lowdose of the next antipsychotic. sometimes when choosingfrom one medication to another, it's hard to know the relative-dosepotencies of these medications. you end up underdosingor possibly overdosing the patient on the new medication. the other major one is when you gofrom a sedating antipsychotic to one which is not sedating. the patient is generally very thankfulfor that, that they're not very sleepy. but that can be alarming,or some behaviour can come through

in a patient who is no longer as sedateas they were before. there are some individual difficulties,but they're the two general situations. geraldine: chris? if i could add another point in relationto the so-called cross-taper, the other issue we're dealing with is the notion oflong-acting risperidone injection and the introductionof the risperdal consta. it's important to make the point thatthe full effects of consta really aren't going to be evidentfor five to six dosage intervals

after the introduction of the drug. we're talking three or four months. there's a need to continue the initialantipsychotic therapy that you've started with until you've gained some of the effectsof the long-acting risperidone and they've become more evident. that's an important pointto bear in mind. it also brings us back to the notion about when you starta long-acting antipsychotic drug.

very important to emphasise thatwe don't kick off with one of those. - it takes too long to kick in.- always oral first. can you give us an idea of whyyou're mentioning that? in clinical practice, are you seeingpeople not waiting that period of time? the expectation is,they've had an injection, perhaps they've come back for theirsecond injection a couple weeks later and people think,i've got them stabilised, they've had no untoward effects, it's time to get rid ofthe first antipsychotic.

they're almost frightenedof having two drugs going at once. in an ironic sense, they're probablydoing that patient a disservice by not continuing the first druga little bit longer. although, if i could talk froma general-practice point of view, bombard is probably not the right word, but medical and pharmaceuticalrepresentatives give us the impressionon all this range of new drugs, in particular with antidepressants, that you can stop oneand start the other the next day.

when you look at the guidelines,it's probably not true. that's another reason i get fearfulabout these things. to judge one side effect as being eitherthe old drug or the new drug is then undoingthe therapeutic relationship that you might otherwise have got,so very important. this goes very wellinto the drug-interaction issue. a lot of that might be that the drugsare acting on each other. christine,would you like to comment on that? drug interactions area really interesting area

because they're never absolute. there's always exceptionsthat make the rule. the thing about drug interactions is knowing which drugs arelikely to interact, determining in a clinical situation whether this is a reasonable thingto go with or not, knowing whether the interactionis serious or not, and if it is a potentially seriousinteraction, whether this is still an acceptable riskin a clinical situation.

if you do go with that decision,knowing what symptoms you're looking for as early signsthat something is going wrong. you need to make sure thatthe practitioner prescribing understands the potential interaction. you need to know that the patientor their carer has an understanding of what you're looking for,and that they will seek early treatment if any of this occurs. if you can't ensure that safety, you'vegot to seriously think about whether this is an appropriate way to go.

it's relatively easy to get informationon drug interactions that we know about. but there are still drug interactionsthat we don't understand, or occur so rarely that we don't haveenough information on them. there might be drug interactionsthat haven't as yet occurred, and we still need to find outabout them. so don't just exclude thatfrom what's going on. just because a patient tells yousomething that's never been said before, doesn't make it untrue. there's a question about the useof anti-anxiety benzodiazepines

that perhaps i can direct to you,anthony, from a gp in south australia, asking whether there's ever a rationalefor using more than one benzodiazepine in combination at a timein the same patient. very rarely, i'd have to say. benzodiazepines havedifferent characteristics according to their half-life. there's really not huge gainin having multiple defence. it fits in with your message about,keep it simple, avoid polypharmacy. on this point about drug interactions,i wanted to mention cytochrome p450.

anthony, in your specialty practice, doyou guys talk cytochrome p450 language? we occasionally intimate, thoughi must say we're not full initiates... geraldine: you're not fluent?- ..into this... (speaks indistinctly) the point is,if i see a new combination, and because of the increasing numberof psychotropic medications, there are lots of potentialinteractions, i just check. it's the easiest thing to do. ring up the drug-information people. anthony: it's online,it's in guidelines.

can i also say for the gps out there, they're sitting there,usually with a computer that is going to tell themwhat the interactions are. i know from personal experience,and this is not a good thing to admit, that you click that button and say,yeah, i know that one. but if you don't read it, if you don'tunderstand it for your favourite drug, there's a lot of cytochrome p450 systemsout there that we don't know, in a general-practice sense, what they really do. we don't take notice of them.

we do when it comes tothrowing up a message in front of us - don't use azithromycinwith this or fluconazole with that. but that's about as far as it goeswith different antidepressants. geraldine: chris,did you have a comment? it's a matter of understandingthe basis for the interaction, anticipating it in advance, and knowingwhat to do in terms of monitoring. i thought you might be interested inan example we had just recently. a person came into hospital who had already taken simvastatinfor their lipids.

somebody decided this person neededa trial of fluvoxamine, luvox, knowing that the luvox isgoing to inhibit the 304, the enzyme that is responsible forsimvastatin metabolism. we measured serial cksand watched them start to rise, said, this is the time to stopand think about something else. we could see an interaction evolvingand we were able to manage it. that's an exampleof what can be achieved if you do understandthe basis of the interaction. that's probably the point.

we know fluvoxamine isa potent inhibitor of enzymes that cause drug interactions, so you could prioritise your concernsto those sorts of drugs. one of the other priorities, anthony,might be patients of ethnic backgrounds. there's a lot of discussion thatthe genetic polymorphism that leads to differentdrug interactions is from your ethnic background. we're going into the areaof personalised medicine, which will be coming our way.

there are certainly different geneticloadings for the different systems, not just for cytochrome p450. also different susceptibilities tothings like experimental side effects, or even agranulocytosis from clozapine. this is increasingly an areawe have to keep our eye upon as we learn more about the geneticdiversity within our population. but it's real. our rural colleagues might need to thinkabout aboriginal susceptibility here. do any of you have a commenton indigenous australians

and their sensitivityto adverse drug reactions? sadly, a very understudied population. there's not the research that's going toinform us well in that area. but certainly, there appear to bedifferent susceptibilities. i should also mention there aredifferent responsiveness factors amongst different populations as well. some people do much betteron particular treatments. i think the futureof personalised medicine one day will be understanding a better basis forthe genetic components of the illnesses

and being able to tailorthe selection of the medicines in the direction that willgive best results. and avoid adverse reactions? - quite possibly.- fantastic. why don't we move onto our next case study? a younger patient, trent,who is 12 years old, and he's depressed. his mother has brought him to the gpbecause she's expressing concerns about his moodand inability to get out of bed, but she's concerned that she doesn'twant to use medication in young people.

jonathan, you would have this situationpresent sometimes, i expect? i have to say thatapart from this case study, i tend not to see 12-year-oldswho are depressed. that's not to say one might notwalk in the door tomorrow. chris: yeah, that's right. i'd have to say that my gut feelingwould be to question the diagnosis, or to understand what is the problem. that goes a long way to whereour paediatric psychiatric colleagues really do have an understanding here.

i'd be most uneasyin suggesting anything other than non-pharmacological therapyat this stage, and be asking for a referral. i'd want to question the diagnosis. at the end of the day,i'm always aware of the old adage of treating children,in these circumstances, where you're on your own. nobody necessarily supports you,nor do they say you did the wrong thing. so i think getting some good informationfor mother.

trent is 12, but maybe he's a mature 12. the most important thing here is to see if you can get trentto understand what his illness is. - to participate.- i admit again, i'm a gp, i'm going to handballstraight to anthony. jonathan, i think someof your gut reactions are very right. the evidence doesn't support the useof antidepressants in12-year-olds anywhere near as strongly as later,in adolescence, or in adult life. the older you get, the more likelythe antidepressants are going to work.

that diagnostic clarification to look atnot only trent but his mum, the stresses in his life, look at what is happening for himis very important. after that, the first port of call isdefinitely psychological treatment - cognitive behavioural therapy would bethe treatment of choice for trent. pharmaceutical interventionswould be down the line. one reason why this mothermight have been concerned about the use of antidepressants is allthe information that's been in the media about suicide associated withantidepressants in a young population.

could you please assist us inunderstanding what this risk really is, and whether some antidepressantsare safer than others? yes. well, this has come out ofthe various investigations and trawlings of pharmaceutical companiesin their large drug trials with ssris. the first thing to rememberis that overall, the risk of committing suicideis far less after you start an effective treatmentthan before it. in trials looking at overdosesor self-harm, those rates are higher in the monthsleading up to starting treatment

- than in the months after.geraldine: that's an important point. nonetheless, there is a small groupof people who have difficulties, particularly with the ssris,with agitation or akathisia secondary to those medications. if that particularly affectsthe young person, there is the risk thatthat added agitation would lead to self-harmor a suicide attempt. some of our viewers arein rural locations who may not have accessto non-pharmacological therapy

and feel compelled to putthe young person on an antidepressant. what advice can you giveon monitoring for the risk of suicide? firstly, it's important to be honestwith both the parent, who's going to be worried and probablygoogling the information anyhow, and the young person in question. so, to say that your expectation is thatthis medication will help them, but there is this chancethat for some people, there's an increase in agitationor anxiety. if you saw that,would you immediately stop medication?

not necessarily.this might be one of the areas in which a short course of benzodiazepine to helpsettle that agitation might be useful, or to halve the tablet. although the ssris have been marketedwith a one-tablet-fits-all, there's no doubt that sometimes half a tablet is the doserather than a full tablet. cutting the dose may be the wayof dealing with that particular problem. jonathan: can i ask a question? if we move forward in trent's lifeand make him 19 or 21,

is the same risk of suicide still there? the problem with treating depressionis the risk of suicide is always there. that's an unfortunate but important factto recognise. the risk assessment must be part ofwhat you're doing. not only are you looking forthe symptoms of depression, you're also asking questionsabout thoughts about self-harm - have they thought of any techniquesthey might use to hurt themselves, have they got comorbidsubstance-abuse problems, have they had a past historyof trying to hurt themselves?

so getting an idea about the risk. that also helps form a plan for how you're going to treatthat young individual, what other resources you'll pull in -family, friends, how many tabletsyou write on the prescription. certainly there's no doubtthat ssris are safer in overdose than the older tricyclicsor venlafaxine for that matter. do we have a black-box warningthese days on these things, and if so, do we have an age limit?

there's certainly a black boxon the ssris. it was one of the first classesto get a black box in australia. - yes.- chris? on the epidemiology of suicidein australia, and it's a sad thing to have to study, it's important to note thatit's really changed quite a lot since the introduction of someof the newer, less toxic drugs. the majority of suicidesthat complete in australia are self-inflicted violence -hanging yourself, shooting yourself,

jumping from heights,followed by carbon-monoxide poisoning. drugs are a distant third,and the drugs that are used tend to be oftentimes non-psychotropic drugs -street drugs, analgesics, anticonvulsants, those sorts of things. so the things to watch forhave probably changed. the other thing i'd just point out, if you're dealing with somebodywho's at very high risk of suicide during initial treatment, the placefor them to start is in hospital. on that cheery note...

- i think there is a cheery note.- oh, good. with the increased useof antidepressants, suicide rates that had been going higherthrough the '90s have turned and have been trending downwardsover this decade. the increasing use of antidepressantsis probably having an effect. well, our next case study examinespsychotropic drugs in the elderly. amy is an 83-year-old woman who isa resident in a private nursing home. she's on rivastigmine for mild dementia, and she's been on warfarinfor some time.

due to behavioural problems, she wasrecently prescribed risperidone. since then, amy has complained of sleepproblems - trouble falling asleep, frequent waking, nightmares,nocturnal leg cramps, and she's wandering around at nighthitting other patients. she has also been incontinent of urine. jonathan, this is one of your patients. it's not an uncommon scenario, is it? no. i probably get a callto a nursing home once a week for fairly similar problems.

whilst they aren't all on rivastigmineand warfarin and risperidone, in fact,a lot of them are on risperidone after i've been to the nursing home because the nursing staff areunderstandably pulling their hair out about what to do with amywandering the corridors at times when they can'tstaff the nursing home. they've got a duty of careto look after people. so the chemical restraint ideais not such a bad idea. we all know with dementia in particular

that there's a behavioural-disordersaspect. risperidone can be indicated for that. the first thing i would do if i was called to see herand hadn't put her on risperidone, or even if i had, perhaps,would be to stop it again. maybe some of the side effects,especially being incontinent of urine, would probably be related to that. the fact that she's got crampsand waking up and having poor sleep maybe is due to the rivastigmine.

my first impression would be thatthere's a combination of drug reactions, and i'd be keen to figure outwhat to do about that. i might comment to two peoplein this situation. instead of just throwing itto my colleague anthony, i might even ask chris as a pharmacist to do a residential-medicationmanagement review and say, i doubt she's only on warfarinif she's on warfarin. there's probably other drugs, and therecould be more confusing things. having said that, i'm sure i would havechecked a lot of reversible causes -

urinary-tract infection, et cetera. but, chris, i'd probably ask. if she's only on three drugs, that may go a long way to explaininghow she's made it to 83. having said that,she's on three crackers, isn't she? i worry when i see warfarinin a nursing-home patient with a dementing illnessand on antipsychotics. you always worry about falls. subdural haematoma is somethingyou have to concern yourself with.

there's a lot of debate about the rolefor antipsychotic drugs and the managementof behavioural dementia, whether or not they do indeedincrease mortality. clearly there's evidence to saythat they do, but you have to ask yourself,compared to what? if they weren't getting antipsychotics, or some form of pharmacologicalassistance with their agitation, what would their outlook and prognosisbe like? i suspect quite similar.

the evidence now to say that these drugs cause a greater incidenceof cerebro-vascular events than their predecessors isstarting to look a bit shaky. i suspect the risk is pretty similarfor most of them. would you be suggesting intermittent useof risperidone in any way, or is continuous use more effectiveand therefore safer? there's a point for debate. you hear different schools of thoughtenunciated. one is to think that the answer isto provide some facility

for nurses in the care setting to be able to choose smaller dosesof the drug, or to omit doses if they're not needed, and to try and reduce the longitudinalburden of psychotropic drugs that amy has to carry around,going forward. but there are different waysof looking at it. i'm sure there aredifferent schools of thought. the dose of risperidone isclearly important. if i was starting risperidone,i'd be starting, as we said,

with a sniff of the bottle. but a very low dose. the other question is, the stroke riskrelated to risperidone itself as opposed to the anti-stroke propertiesof warfarin, how much are you robbing peterto pay paul? we have a faxed question froma mental-health nurse in queensland, who says,'it can be difficult with antipsychotics to tell side effects from symptoms. are there are any guidelinesin working this out?'

anthony,have you got any magical guidelines? this is a very important issueand quite complex. it is a very important issue,especially when it's common for people to be on a numberof different psychotropic medications. i suppose, chris, i'm of another schoolon that particular issue, and that would be to have a small amountof medication given on a regular basis, and bevery cautious about increasing it. that also applies to the questionthat's come through. it's very hard to know where you're at

if different medicationsare given at different doses the night before,according to the perceptions of nurses that are seeing that patient. an appreciation of the effectsand side effects is easier if there's some consistency in what hasbeen given to the individual patient. as to, is there a guide for which isside effects and which is effects, that comes down to having a clear ideaabout what you're trying to treat. does it require clinical judgement and appreciation ofthe course of the illness?

it does. it also requires youto lay hands on the patient. you have to see whetherthey've got that rigidity. you have to have an ideaabout their postural blood pressure, whether you're causing that to drop and whether that's going to cause themto fall. understand too that these peoplehave difficulty in some cases verbalising or describingtheir symptoms. it's important not to overlook the fact that these people might be hot or coldor tired or hungry or thirsty

or annoyed or sad or the gamutof emotion we all experience, but they're unable to say those thingsthe way you and i can. the other thing that comes to my mind is the time course of the behaviouraldisturbances that you see. it's going to change over time. it's not a consistent thing. it's important,if you are prescribing medication, whether it is or isn'tcausing side effects, to actually reassess the situationfairly frequently.

patients' symptoms do change over time. dementing illnesses are degenerative, so you do see fairly well-staged changesin behaviour. what's appropriate now might not bein three to six months' time. you do need to make sure you've gotthat follow-up and review going so you're not unnecessarily medicatingpeople along the way. i'm not advocating that you don't usea treatment when appropriate, but don't use itif it's no longer needed. all of that is very wisely said.

our final case study for this eveningis nick. nick is a 26-year-old man who was diagnosed with schizophreniawhen he was 20. he had been previously violentand aggressive and had attempted suicidea number of times. he's been prescribed olanzapine,but he's not been taking it lately. he often drinks heavilyand has been frequently using cannabis. one of the issues with nickis also that he's non-compliant. anthony,could you comment on this vexed issue

that's so difficult to managein practice, but it is an areayou've spent some time in. what are the issues, and how do wedeal with it in terms of drug safety? nick's situation is all too familiar,unfortunately. it really does come down togetting him an effective treatment which he is able to take. that really depends ona number of other things - the support you can get to nick, whether there are people thatcan help monitor his medication

or check up on that safely and without provoking huge amountsof family discord or things like that. it sounds as if nick may havehad a reasonably long course of his psychotic illness. for people in his situation, a trial ofclozapine should always be thought of. clozapine is the most effectiveof the antipsychotics. it also has positive benefits from the point of viewof ameliorating substance abuse and decreasing suicidality.

there are some real benefits in prescribing an antipsychoticlike clozapine despite its many side effects. however, it's a tablet,and as chris said, treatment is only effectiveif you actually take it. this can be one of the vexed issuesof getting an antipsychotic appropriately for the patientin a way which actually gets to them. that may mean a depot medication and some formof community treatment orders.

one of the things that can contributeto non-compliance, non-adherence, particularly in this population,is sexual dysfunction. could you please commenton what the implications might be and the comparative frequencyof this side effect in the differentpsychotropic medications? nick is a young man,and young men really are interested in a relatively small number of thingsat times. sexual dysfunction is a real problem, particularly for antipsychoticsthat raise prolactin,

so, high-potency antipsychotics,and for the ssris. they can be a problem acrossthe whole range, but in particular, they are the drugs that are well knownto cause these problems. the difficulty is finding out, knowing. it's something that, in my experience,you have to ask. - they won't tell you?- they won't necessarily spontaneously revealthat they have sexual problems. geraldine: how do you ask the question? it's good to know your patientin this particular thing.

i would commonly lead up to itfrom the point of view of girlfriends. if i know they have a girlfriend,or to ask them, quite baldly at times, that one of the reasons whypeople stop medications is they have problemswith sexual function or impotence, and going through those words. often, that is one of the issuesfor non-compliance. right. jonathan, in your practice, have you had to deal with young peoplelike nick being non-compliantwith their psychiatric medication?

not as much. the community treatment ordersare usually invoked at this stage in order to get them into areas wherethey're more likely to be compliant. however, one of interesting thingswith this is that he has hepatitis c. i think we left it out in the end.too complicated. anthony: we can add it now. i suspect if you looked at a lot ofschizophrenics in younger populations that they are hepatitis c-positive. one of the ways, maybe, to gain somedegree of consistency in his treatment

would be to suggest thathe gets treatment for his hepatitis c. one of the spin-offsmight be that your clinic, if you're able to providethe regular weekly injections, is to be able to work him througha process of coming along. by doing that, it's possible we could then get himonto a depot at some stage. that would be where i would seea general-practice aspect to this case. one of the issues you're raising there is that medical illnessesare very common.

in fact, they're more commonin this group of patients, in people with mental illness full stop,than in other groups in the population. that flows throughto increased morbidity and mortalityfor this particular population group. working with general practiceis a very important thing. this is one of the problemswith our health system, is that we still have some very basiccommunication. a more overt reason for non-compliancewith these medicines, especially in young people,but in all ages,

is the metabolic syndrome you alludedto at the beginning of the program. if these medicines make you fat,you're not interested in taking them. are there medicines aroundyou're adding in as polypharmacy, but might helpwith the weight-gain issue? i've heard some people use,is it lamotrigene? - topiramate.- that's it, topiramate. i suppose i would go back and look at particularly the antipsychoticswe're talking about here. there are antipsychotics now that havea very low risk of causing weight gain.

there are some that are well identified as being very likely culpritsfor the weight gain. you're trying to choose the oneswith a lower likelihood. going back to diet, exercise, these arepeople who are often very neglected and who stay very muchwithin an isolated existence. trying to bring them outwith some psychosocial program, some rehabilitation or recovery program,is very important. other pharmacological approaches are, metformin would be onewhich is used on occasions.

but really we're talking about the foodthat goes in, which is oftenof an appallingly low quality, and too little exercise and too longspent sleeping on the bed. would that be the samefor the weight gain that occurs with the older drugs like tricyclics? something like exerciseis a useful intervention, or metformin? again, first go back to the other partsof the equation, which is putting on the weight. it might be that a changeof antidepressant,

if that's not going to destabilisethat person, or, good heavens, reviewing themedication the person has been on for perhaps many yearsis a good idea at this stage, and seeing if there are other waysof approaching that problem. with the increasing availability of somany different drugs, we have options. christine, did you have a comment? i had a comment about psychotropicsin general. across most of the drug categorieswe have, there's a reasonable number of drugsthat are implicated

in causing significant weight gain, and doing it in a relatively shortspace of time. there's also a significant number who might not cause you to gain weightin the short term, but over a longer period of time,you see similar sorts of changes. some of the ssris, for argument's sake,short term, you're looking at relative weight lossesor being relatively weight-neutral, but long-term use, you might seesignificant weight changes. given that this population as a ruleare generally very poorly cared for -

their self-care is fairly poor, theiraccess to services is relatively poor, their identificationof general medical illnesses is poor and the follow-through is poor - it's important that you put in placethe psychosocial stuff across the board. it's not just antipsychoticsor just the old tricyclics or just mirtazapinethat causes weight gain. across the board we see it. that's very, very true. the issue though is thatwe have a rural audience tonight.

maybe in placesthat are non-metropolitan, it's not so easy to accessthose sorts of services. what about telepsychiatry? how accessible is that now to people whoneed non-pharmacological interventions? can they get it over the internet? certainly there are some good programsin the areas of anxiety and depression, which are widely accessibleover the net. geraldine: like the programson beyondblue and so on? beyondblue is a good place to startfor those programs.

google depression, and it will come up. the availability of telepsychiatryvaries greatly from place to place in australia. i'm sure our viewers have a much betteridea about what they can get than i do. jonathan: that's not our big australian,is it? the one that starts with t, ends with aand has 'elstra' in the middle of it? it all depends on where you are,what services you can access. before we go to our take-home messages, i wonder if any of you think there areburning issues we've forgotten tonight

or still need to bring up? there's so much we have to cover.it's such a huge area, isn't it? we've dealt with paediatrics,geriatrics, pregnancy. one of the things i'd like to brieflytalk about is compulsive gambling as an issue associated withsome of the parkinson's drugs. have you seen that with any ofthe other drugs that affect the brain? i haven't myself. but i suppose gamblingis one of those behaviours which is there with substance abuse

in the background of manyof our patients. it's a matter of asking that question which will unveilwhat is a real problem. for me, the thing we haven'ttalked about is that comorbidity, the fact that one conditiongoes with another condition, which often goes witha substance-abuse problem. getting a handle uponthose multiple different problems is a challenge at times. you should always inquire aboutthose other areas of illness.

on that note, we might hearyour take-home messages tonight. jonathan, what would you like to say? my first take-home message is,ensure the correct diagnosis. we've heard tonight thatthere's lots of different medications for lots of different problems. understanding that you are confidentin your diagnosis is one of the most important things. the second thing is to be familiar witha particular drug in each class, whether it be the ssris,whether it be the snris, the nassas.

all these different acronyms,but they mean something. we've heardthat it's very important to understand the prescribing informationrelated to them and how they interact. most important. chris? it's an old message, but it's -first, do no harm. be conservative. think carefully aboutwhat you're choosing in terms of the dose of the drugsthat you use, the wayyou're going to combine them together,

the monitoring you're going toput in place for the patient to ensure you pick up on adverse effectsas they evolve. also, it's very important notto let that conservativism prevent you from using medicationswhen they're very clearly required. don't hesitate to use medicineswhen they are needed. christine? as jonathan said,it's important to know your drugs and what you're actually prescribing. and being aware that

we're forever getting new informationabout medications. what was good yesterdaymight not be good today. we need to keep up to date with that. if you don't keep up to date,you need to know where to go to get the information when you need it. so, making sure thatyou either do your reading or you know where to getthe new information to make sureyour information is current. - very true. anthony?- i'd say try and keep it simple.

try and minimise the numberof different drugs people are on. if one isn't working, then stop itand trial another one. the best wayof avoiding drug interactions is using psychological treatmentsif you know how to or if that is available to you. i'd like to thank you allfor participating tonight, jonathan, chris, christine and anthony. i hope you've enjoyed this programon psychotropics, what's safe and what's not.

if you're interested in obtainingmore information about issues raised in the program, there are a number of resourcesavailable on the rural health educationfoundation's website at: don't forget to complete and send in your evaluation forms, and please register for cpd pointsby completing the attendance sheet. finally, our thanks to the departmentof health and ageing for making the program possible.

thanks also to you for taking the timeto attend and contribute. i'm geraldine moses. goodbye�