354 \200 D. Schwarz; Chipmonka y r t a h c y s P i consider a tighter range if elderly ( \200\200 sensitivity to Li+ neurotoxicity).244 355 Helping those with mania and a high risk of suicide \200\235 s s e n l l e w n i d a e d l e e f Risk of suicide is high if: \200 Previous suicide attempt \200 Family history of sui- c ide \200 Early onset of bipolar disorder \200 Extent of depressive symptoms (eg hopeles sness) \200 Increasingly bad aff ective signs \200 Mixed aff ective states \200 Rapid cycling \200 Abuse of alcohol or drugs.245 Lithium reduces risk of suicide.245 If contraindicated, olanzapine + \202 uox- etine may be better than lamotrigine (below).246 \200\207But don \200\231t rely on drugs. Often peop le with mania won \200\231t take them anyway. As one bipolar writer said \200\234I do not believe that a complex problem can be solved simply by pop- ping pills \200 I thrive in the extremes of my cycles, and the words pour from my mind and hand. All that evaporates in we llness,1 so I imagine it would dissolve completely if I chemically alleviated my malady. I will not dilute my intensity and drain my writing. I feel dead in wellness, so I fear that I would feel just as lifeless if I was \200\230cured. \200\231 My identity is also still s o blended with this disorder. It is a fundamental part of me and shapes my world. I accept this disorder as a forming force in my life and value how it has made me. It tested me; it made me stronger; it made me diff erent; it gave me my creativity \200 It is not just a dis ease to be remedied; it is a real part of me that I need to learn to cope with and adapt to . I need to discover how to control it, rather than allow it to dominate me so that I can l ive with it as a vital aspect of my life. \200\235247 Cognitive therapy (p373) is of great value in helping people (who retain some insight) ride their cycles without falling off .24 6 I \200\234 : e r u c d n a e s a e s i d f o s a e d i y r t a i h c y s P s t r e v b u s s g o l B When lithium does not give good control Note that abrupt cessation of lithium precipitates acute mania in up to 50% of patients. Discontinuation should be gradual over 2 \200\2234 we eks. Anticonvulsants: Semisodium valproate (SE: hyperandrogenism if \200 ) and carbamazepi ne (400mg/8h PO; swallow whole; do not chew) are next steps.248 Some authorities say most s peci \201 c indication may be in rapid cyclers ( \211 4 acute mood swings/yr). Lamotrigine may be as good as citalopram in bipolar depressive states.249 Antipsychotics: Olanzapine h as a role.250 In one meta- analysis, there was no diff erence in overall effi cacy of treat ment between haloperidol and olanzapine or risperidone. Some evidence suggests that halo- p eridol could be less eff ective than aripiprazole.251 Anticonvulsants such as lamotrigine, gabapentin and topiramate are po- tential mood stabilizers. Lamotrigine has the strongest evidence.252 Combination treatments : (Often tried). Lithium plus carbamazepine may be synergistic.253 Lithium (or valpoate) pl us an atypical antipsychotic, eg risperi- done or olanz apine may help if unresponsive to m onotherapy.254,255 Antidepressants with lithium Lithium (or an alternative mood stabilizer) reduces risk of mood \202 uctuations from mania to depression in people with bipolar aff ective disorder. For depression occurring during lithium treatment antidepressants can be used: selective serotonin reuptake inhibitors (SSRIs) bupropion, and venlafaxine are said b y expert committees to be best. Ta- per from 2 to 6 months after remission to minimize mani c relapse.256 Consider monoamine oxidase inhibitors for anergic (=lacking in energy) bipolar depression.2 57 ECT also has a role (p342),258 and meta-analyzes support use of omega 3 oils (only for w hen mood is low).259 \201\2011 A counter argument from the periodically depressed poet Thomas Krampf: \200\234 one can have a vision but no vision is worth anything if one is too sick to implement it \200\235 \200\224 and many writers have found their creativity \202 ourish more when treatment is underway. M Berlin 2008 Poets on Prozac, Baltimore. Schizophrenia: current concepts Schizophrenia is a common chronic/relapsing condition often presenting in late teens/early 20s with psychotic symptoms (hallucinations, delusi ons); d is- organization symptoms (incongruous mood, abnormal speech and thought); negative symptom s (apathy, self-neglect, blunted mood, \200\201motivation, with- drawal); and, sometimes, cognitive impairment.260,261 It has major implications for patients, work and families. Inc idence: 0.15 : 1000/yr. Prevalence: 1%. What \200\231s in a name? Some experts hold that the term \200\230schizophrenia \200\231 has out- lived its usefulness as it implies that a ll people with schizophrenia have the same pathology \200\224and hence need antipsychotics. A more nuanced approach is to avoid diagnostic labels, certainly for the 1st 6 months, and not to use anti- psychotics automatically. Dopamine dysregulatory disorder (BOX)262 is a n ew name \200\224without the pejorative overtones of violence, fear and unpredictability. A word on \200\230psychosis \200\231: In its \202 orid form, psychosis is the archetype of the layman \200\231s \200\230madness \200\231 But, the usual picture is less obvious: the patient may be sitting alone, quietly attending to his or her voices. If hallucinations, d elusions, or a thought disorder (de \201 ned on p358) are present, the cause \200\230must \200\231 be either schizophrenia and related disorders, a disorder of aff ect (mania or de pres- sion or both, p336), or be organic (eg drug misuse, head injury). So the term psychos is is not in itself a diagnosis, but is a useful term to employ, while the underlying diagn osis is being formulated. Beware labeling people; remember that even during the best of tim es, only a thin veil separates us from insanity. Genes & environment Many genes implicated in schizophrenia also \200\200 risk of bipolar disorder. 253 \200\223265 International Sch izo- phrenia Consortium Some are susceptibility genes (needing environmental triggers). Gen ome-wide studies point to a gene coding myosin on chromosome 22 and a region of >450 gene v ariants, in the major histocom- patibility complex (MHC) region on 6p. The dysbindin gene o n chromosome 6 is important too. Early use of cannabis is a trigger: those with VV homozygo sity of the catechol-o-methyl-transferase gene (COMT; risk \200\200 \211\21010 compared wi th mm variants). The timing of triggers is important.266 Those starting cannabis at 15yrs o ld are 3 \211\210 more likely to develop schizophreniform psychosis.267,268 Is schizophreni a a neurodevelopmental disorder? People with schizo- phrenia may suff er unusual neurodevel opment either through inheriting genes and/or some insult to the brain that impairs its dev elopment. This leads to subtle cognitive and behavioral eff ects in childhood269 and then p sychosis at or just after adolescence. Relevant prenatal/obstetric events: early rupture of membranes, gestational age <37 weeks, incubator use, winter births).270 MRI shows diff ere nces in the brains of those with schizophrenia (and their 1st degree relatives271): eg larg er lateral ventricles, reduced frontal lobe and parahippocampal gyrus. Reduced (particularl y on left) temporal lobe, hip- pocampus (subserves memory/emotion) and amygdala (involved i n expression of emotion). MRI has shown diff use reduction in cortical gray matter associat - ed with poor premorbid function.272 NB: use of psychotics may also cause brain shrinkage \200\224eg up to 20%.273 However, schizophrenia also has an onset later in life, particular ly women over 30.274 It has been estimated that about 40% of people who develop schizophren ia have a developmental problem, but the majority are not remarkably diff erent from the ge neral population and have no cognitive de \201 cits. So what are the other pathways that l ead to psychosis? Social factors: Being brought up in cities increases the risk of schizoph re- nia (UK incidence is particularly high in London), and there are higher levels of schiz ophrenia in migrant groups such as Asians and African-Caribbeans (?mechanism through social adversity, racial discrimination, social isola- tion).275 The associated \200\230stress \200\231 on the brain has been suggested to aff ect the morphology of the brain via hormona l in \202 uences as well as the stress of being psychotic resulting in high cortisol level s causing further brain changes. 356 Prevalence: 0.3 \200\2230.66% \200 y r t a h c y s P i 357 Physical and metaphysical insights into schizophrenia Auditory hallucinations One idea275 i s that there is misreading of inner speech. If you think of your favorite poem, you can pro duce its words in your mind, but you know that you produced them. A person with schizo- phr enia produces words in the mind in a similar way but then may mis- interpret them as coming from an outside source. We know that during hallucinations, muscle activity resembling pho nation is detectable in the tongue. Sub-vocal speech can be picked up from the larynx, and this may correspond to what the hallucinations are telling the patient to do. We know that during inner speech Broca \200\231s area is activated, and imaging stud- ies show that audi tory hallucinations activate Broca \200\231s area, indicating that they result from misattr ibuting inner speech. But why do suff erers not real- ize it is their own inner speech? She rgill has shown that during auditory hallucinations there is also activation in the auditor y cortex, temporal lobe and subcortical areas.276 This re \202 ects the activation of a sy stem used when we are listening to external speech but not to our internal speech. This is why some minds are tricked into thinking the words come from outside. Dopamine dysregulatio n and aberrant salience Whatever increases do- pamine worsens psychosis, while blocking dop amine helps treat psychosis. Dysregulation of mesolimbic dopamine underlies the positive sy mptoms of psychosis. Dopamine mediates our attachment of salience or importance to ideas an d objects hence excess mesolimbic dopamine leads to attaching sa- lience to all sorts of un related phenomena. Suff erers cannot have a rational explanation and instead create what se ems to them a convincing explana- tion: it is this we call a delusion. Note that the best p hilosophers (eg David Hume, 1711 \200\22376) show that the notion of causation is based on just such a delusion: there being no true or demonstrable connection between cause and eff ect \200\224just a relationship that exists between ideas in our minds. Any being that has this power of making causal connections (attaching salience to unrelated events)277 has ada ptative advantage, but is a hair \200\231s breadth from psychosis. It is in this \200\230h air \200\231s breadth \200\231 (opposite) that we run our lives. Without our ability to att ach salience there would be no such thing as love at \201 rst sight \200\224maybe no love at all. Our humanity and our tendency to psy- chosis are two sides of one coin. This is wh y we owe the mentally ill an especial duty of care: they are suff ering for what makes us h uman. Antipsychotics reduce the underlying dopaminergic drive and this attenu- ates the abn ormal attribution of salience. So people stop hallucinating or they stop thinking their nei ghbors are persecuting them, but they still be- lieve that last week there really were voic es telling them to do things. How do patients explain what is happening? Mental illness may seem unfathomable; for others the turmoil of a \200\230mental breakdown \200\231 is later seen as a \200\230mental breakthrough \200\231: we need to see purpose in all things, inc luding our mental illnesses. Quote from a blog, from a man with schizophrenia: \200\234I w as a passionate, devout Christian and believed I had found ultimate truth. A snowball of od d tragedies struck, which turned things around making life an inner hell. The powerlessness of not being able to cope with it all led to deep depression as well. I thought my life wa s truly over \200\235 (an awful lot happened in these dot-dot-dots \200 but things did g et better) \200\234 \200 I attained a level of transcendence and awareness that I never ha d before. My cogni- tive, writing, speaking, communication, insight and understanding abili ties suddenly reached a level on their own. It was then that I was able to under- stand hig her spiritual truths. So I was wondering then. Perhaps my soul or higher self wanted to evo lve to a higher awareness level and when it was in the process of doing so, my physical bra in had trouble adjusting to it, so it started mis \201 ring and malfunctioning, which crea ted those obsessions and delusions. Perhaps that is the reason behind some mental illnesses . \200\235278,279 t u o y a w e h t t o n s i g n i n i h p e h T y r t a i h c y s P . \200\235 d e s s e s o p g n t t e g \200\234 t i l l a c I r e v o e k a t s e c i o v e h t n e h W : e r e h p s g o l b e h t m o r f s n o i t a n a l p x e d e l i a f f o a i n n e l l i m 3 Schizophrenia: diagnosis Schizophrenia entails distorted thinking and perception, eg delusi ons and hal- lucinations. These are common, eg in 1) Aff ective psychoses (depression, bipo - lar disorder); 2) Substance abuse psychotic disorders (eg alcohol, cannabis); 3) Psychosi s due to a medical disorders (eg brain tumor); and 4) Schizophe- nia-like non-aff ective di sorders (brief psychotic disorder; delusional disorder; schizophreniform disorder).280 When diagnosing schizophrenia look for: 1 Thought insertion: \200\234He \200\231s is putting i deas into my head \200\235 Thought broadcast- ing: \200\234People overhear my thoughts \200\235. Thought withdrawal: \200\234Thoughts are being taken out of my head \200\235, or repeating of thoughts \200\224 cho des pens es. 2 Delusions of control, in \202 uence, or passivity, clearly referred to body or limb movements or thoughts, actions, sensations. Delusional perceptions (a rare non-ICD-10 example is perception broadcasting, eg \200\234I am a webcam \200\235).281 3 Hallucinatory voices giving a running commentary on a patient \200\231s behavior, 358 \200 or discussing the patient among themselves. 4 Persistent delusions of other kinds that are culturally inappropriate and completely impossible ( \200\234Rasputin has put a transmitter in my brain \200\235). 5 Persistent hallucinations in any modality (somatic, visual, tactile) which oc- cur everyday for weeks on end. y r t a h c y s P 6 Breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech \200\224knight \200\231s move thoughts that change direction, \202 ying off at tan gents, with odd logic, or neologisms (made up words). i 7 Catatonic behavior, such as excitement, posturing, or waxy \202 exibility, negativism, mutism, echopraxia (involuntary imitation of the movements). 8 Negative symptoms (apathy, p aucity of speech, blunting or incongruity of aff ect, eg laughing at bad news) usually resulting in social withdrawal. (1 \200\2235 are co-extensive with Schneider \200\231s 1st rank symptoms of schizophrenia.) Diagnostic guide lines for schizophrenia The main criterion is at least one very clear symptom (and usually two or more if less clear-cut) belong- ing to any of the groups 1 \200\2234 above, or sympt oms from at least two of groups 5 \200\2238. Because many people have brief psychosis-like symptoms, do not di- agnose schizophrenia unless symptoms last for \200\2066 months and sy mptoms are present much of the time for at least one month, and there is marked impairment in work or home functioning. Also, \200\230rule out \200\231 other causes of psychosis (eg bipolar disorder, drugs/alcohol, CNS tumors, head injury). ICD-10 distinguishes the following subtypes of schizophrenia: Paranoid (commonest subtype, here hallucinations and/or delusions are prominent). Hebephrenic (age of onset 15 \200\2232 5yrs, poor prognosis, changes in mood prominent with \202 eeting fragmented delusions and hallucinations). Cata- tonic (characterized by stupor, excitement, posturing, waxy \202 exibility, and negativism). In simple and residual types, negative symptoms predominate. Fr equent symptoms Lack of insight,97% auditory hallucinations,74% ideas of reference,70% para noia,66% \202 at aff ect,66% persecutory delusions.62% Frequent behaviors Social withdraw al, 74% apathy, 56% lack of conversa- tion, 54% anhedonia (inability to feel pleasure), 50% psychomotor retardation, 48% overactivity, 41% self-neglect, 30% posturing odd movement s. 25% Better prognosis if: Sudden onset; no negative symptoms; supportive home; \200 sex (better social integration282); later onset of illness; no CNS ven- tricular enlargement; no family history (data from WHO disability assess- ment schedule283). Overall, only 10% ev er have one episode. With treatment, \211 7% need intensive input/hospital admission for > 2yrs after 1st admission. 28% go >2yrs without needing further hospital admission. Lifetime risk of schizophrenia: 1%. Suicide rates: 10% in acute phase; 4% in chronic. 359 Managing violence (after the Maudsley Prescribing Guidelines) A person can be violent as a result of psychiatric illness, substance misuse, personality disorder, or physical illness. Or it may be the result of adverse ward environments: overcrowding, noise, alienation, and nowhere to go (no blue skies or green \201 elds). This is the danger if sequestration on the ward is the result of withdrawal of privileges for \200\230bad behavior \200\231. \200 Recognize early warning signs: tachypnoea, clenched \201 sts, shouting, chanting, r estlessness, repetitive movements, pacing, gesticulations. Your own intuition may be helpfu l here. At the \201 rst hint of violence, get help. If alone, make sure you are nearer th e door than the patient. Do not be alone with the patient; summon the police if needed. \200 Try calming and talki ng with the patient. Do not touch him. Use your body y r t a i h c y s P language to reassure (sitting back, open palms, attentive). ? s e l c a n a m Get his or her consent. If he does not consent to treatment, emergency treatment can still be given to save life, or if serious deterioration. Use minimum force possible. Rapid tranquillization (RT) is the use of medication in control ling behavior. It should only be used as a last resort when non-pharmacological methods of behavior control have failed. r o s l l e c \200 De-escalation \200 Time-out \200 Placement, as appropriate. \200\201 \200 Off er oral treatment. If the patient is prescribed a regular antipsychotic, lorazepam 1 \200\223 2mg or promethazine 25 \200\22350mg avoids risks associated with combining antipsychotics. Oral options if not already on regular oral or de- pot antipsychotic: (olanzapine 10mg, que tiapine 100 \200\223200mg, risperidone 1 \200\2232mg or haloperidol 5mg). Avoid using more than one antipsychotic to avoid QT prolongation (rapid tranquilization predisposes to arrhy thmias). \200 Repeat after 45 \200\22360min. Monotherapy with buccal midazolam 10 \200 \22320mg d e d d a p n a h t e s r o w o n may avoid the need for IM drugs (unlicensed). \200\201 If 2 doses fail or sooner if the patient is placing themselves or others at signi \201 cant risk \200\224consider IM treatment. Consider the patient \200\231s legal status and consider consulting a senior colleague. Options: \200 Lorazepam 1 \200\2232mg IM (di lute with equal volume of water for injections) Have \202 umazenil to hand \200\223 resp iratory depression. Be cautious if very young or elderly, and those with pre-existing brain damage or impulse control problems, as disinhibition reactions are more likely. e b y a m t i r o \200\224 s e i b m o z Promethazine 50mg IM is useful in a benzodiazepine-tolerant patient. Pro- methazine has slo w onset, but is often eff ective. Dilution is not needed be- fore IM injection. It may be r epeated up to 100mg/day. Wait 1 \200\2232h to assess response. It is an extremely weak dopa mine antagonist d e z i l a n o i t u t i t s n i Olanzapine 10mg IM; don \200\231t combine olanzapine with IM benzodiazepine. \200 Aripipr azole 9.75mg; vs olanzapine it \200\231s less hypotensive but ?less eff ective. \200 Halo peridol 5mg is last-choice as incidence of acute dystonia is high; ens- ure IM procyclidine is to hand. Repeat after 30 \200\22360min if insuffi cient eff ect. \200\201 \200 Consi der IV treatment if an immediate eff ect is needed: Diazepam up to 10mg as Diazemuls over \211 5min. Repeat after 5 \200\22310mins if insuffi cient ef- fect (up to 3 times). Have \202 umazenil to hand. t c e f r e p s e t a e r c \200\201 Seek expert advice from consultant or senior clinical pharmacist on call. Options are limited. IM amobarbital, paraldehyde & ECT have been tried. \200\201 \200 Montor vit al signs every 5 \200\22310min for 1h, and then half-hourly until ambu- latory (if he refus es, observe for signs of pyrexia, hypotension, oversedation and wellbeing. If unconscious, monitor oximetry. A nurse must accompany until ambulatory. Monitor ECG, U&E & FBC if high-d ose IM antipsychotics used. h s o c d i u q i l e h T Schizophrenia: management Don \200\231t dawdle! Delaying antipsychotics worsens negative sy mptoms.284 They can be dramatic, but managing schizophrenia is much more than drugs; it re- quires an individualized care plan that includes psychosocial interventions (eg supported employment with cognitive training) \200\224and support for families.285 Advice and monitor ing Before starting an antipsychotic ask about personal/ family history of diabetes, hypert ension, and cardiovascular disease. Give ad- vise on diet, weight control and exercise. Per form BP, weight, fasting blood glucose, lipid pro \201 le, FBC, ECG if on clozapine or zot epine. Additional 6-monthly monitoring of LFT, U&E, prolactin, weight, HbA1c is recommended .286 Typical or atypical? Typical antipsychotics (chlorpromazine, haloperidol 0.5 \200\2233 mg/8h PO) help symptoms in of those with acute schizophrenia; they are less good for ne gative symptoms. Blockade of D2 receptors is the main reason for their antipsychotic eff ec t \200\224and the cause of side eff ects that often make people stop their tablets. Treatin g extrapyramidal side effects (EPSE) \200 Par- kinsonism: \200\201dose, change to atypic al, or try procyclidine 2.5mg/8h PO; increase if necessary; max 30mg/24h \200 Acute dysto nia can occur within hours of starting antipsychotics. \201\227: Procyclidine 5 \200\22310 mg IM or IV (may take h to work), repeat after 10min, max 30mg/24h \200 Akathisia \200 \224occurs within hours to weeks of start- ing antipsychotics, restlessness may be very dis tressing; so use lowest possible dose or change to atypical \200\224treatment may be needed with propranolol 20mg/ 8h PO cyproheptadine 4mg/6h PO \200 Tardive dyskinesia (chewi ng, grimaces, choreoathetosis) may be irreversible; but try tetrabenazine 12.5 \200\22350mg /6 \200\22324h PO. Symptomatic hyperprolactinaemia: Galactorrhoea, amenorrhoea, oligome- no rrhoea, female/male infertility. Reduce dose or switch to quetiapine. If not tolerated try amantadine 100mg/24h PO; max 200 \200\223300mg/24h PO. Atypical antipsychotics are those ca using no or minimal EPSE. They diff er from one another signi \201 cantly in pharmacodynam ic and unwanted eff ects, which in \202 uences choice. Atypical antipsychotics relieve psy chotic symptoms as eff ectively as typical drugs,287,288 and may lower relapse rates.289 NI CE says to consider oral atypical antipsychotics \200\230in the choice of 1st-line treatme nts Not all trials agree.290 for individuals with newly diagnosed schizophrenia \200\231. W hich antipsychotic? Atypical antipsychotics: amisulpride, aripiprazole, clozapine, olanzapi ne, quetiapine, risperidone, sertindole, zotepine, paliperi- done (a once-a-day drug). Risp eridone recently came top of the list when psy- chiatrists were asked \200\234If you becom e psychotic, what would you want? \200\235127 n=543 Clozapine is restricted to those resist ant to, or intolerant of, other antipsy- chotics (agranulocytosis risk \200\2050.8% in 1st yr of \200\224; specialist monitoring is need- ed). Sertindole is only available on a nam ed patient basis due to signi \201 cant QTc prolongation and fatal arrhythmias.291 Except for clozapine which de \201 nitely causes less EPSE,292 there is no clear advantage for an y one atypical antipsy- chotic over another, so side eff ects are important in tailoring tr eatment to the individual patient. Most unwanted eff ects are dose-related, so \200\230sta rt low in- crease slow \200\231. All antipsychotics \200\201seizure threshold (esp. zotepi ne & clozapine). Special patient groups Elderly, children and adolescents may get more side eff ects. In breastfeeding, most atypicals enter breast milk. Trials of use in pregnancy a re few; weigh up potential bene \201 ts against harm to mother, fetus and neonate. Avoid b reastfeeding. Extrapyramidal side effects (EPSE) are rare with quetiapine293 and clozapine, and uncommon with aripiprazole and zotepine. Can occur at high doses with amisulpride, ola nzapine and risperi- done. Hyperprolactinaemia: Aripiprazole, clozapine and quetiapine have no or minimal eff ect on serum prolactin, olanzapine does at higher doses.294 Sexual dysfu nction: All atypicals can cause sexual dysfunction, eg erectile dys- function, \200\201lib ido, \200\201arousal, anorgasmia, eg from \200\200prolactin (check level)295 and \200 \201semen volume/viscosity;296 retrograde ejaculation ( \200 1-receptor antagonism, 360 y r t a h c y s P i eg with risperidone).297 In one study, 30% had stopped their drugs at some point owing to sexual side eff ects.298 So ask about sex (p328; few will volunteer this information). If e xperiencing problems, adding cabergoline, bromocrip- tine, or amantadine, or switching to q uetiapine may be appropriate.299 Weight gain is common, and \200\201compliance and \200 \200risk of cardiovascular events and diabetes (greatest with olanzapine and clozapine, mod erate with risp- eridone, sertindole, and zotepine; least with amisulpride and aripiprazole ).300 Diabetes mellitus: Prevalence in schizophrenia is twice the expected rate;301 antipsy chotics further increase risk (esp. clozapine and olanzapine). Cardiovascular effects: Olan zapine and risperidone \200\200risk of stroke in the elderly when used to treat behavioral symptoms of dementia.220 Postural hypotension is common ( \200 1 adrenoreceptor blockade). Long QTc on ECG with zotepine, sertindole; fatal myocarditis and cardiomyopathy (clozapine ). Daytime drowsiness: 40% of those on clozapine (30% if on olanzapine or risperidone; 15% if on amisulpride, quetiapine, or sertindole). Managing acute episodes of schizophrenia \200 If acutely disturbed use the rapid tranquillization protocol (p359) \200 Approach p atients with optimism and empathy \200 Provide comprehensive information and consult any advance directive \200 Discuss antipsychotic choice with the patient and start promptly i f distressed and symptoms not tolerable, otherwise refer to specialist in the mental health service (MHS). Dose example: Quetiapine 25mg/12h on day 1; 50mg/12h on day 2; 100mg/12h on day 3; 150mg/12h on day 4; then adjust ac- cording to response (eg 300 \200\223450mg daily in 2 doses; max 750mg/24h). Add-on neuroprotection Case reports & 1 randomized trial give hope that minocycline (200mg/day, as early as possible) can \200\201 negative symptoms. 30 2 Managing risk and psychosocial aspects303 Risk is divided into risk to self, others, and risk of self-neglect. Look at past psychiatric and forensic history. Is there past violence or suicidal or self-harming behavior? Ask yourself where is the patient to be treated? Do they have insight? Can they be managed at home? (via early intervention/home treatment team s), or do they need to be an in-patient (Mental Health Act). Risk assessments are an import ant com- ponent of the management of a person with mental health problems: \200\207p329. F ailure to respond Cross-taper (p369) to a new drug;304 if all fail, combination therapy305 is often tried, eg olanzapine with either amisulpride or risperidone, or quetiapine with ri speridone. In theory, by acting on diff erent receptors ben- e \201 t may occur.306 But of ten it doesn \200\231t go according to plan, and safety issues are opaque. Aripiprazole plu s non-clozapine atypicals may worsen psychosis. \201\201Psychological interventions toward s the end of acute episodes look at treat- ing residual symptoms, eg diffi cult thoughts, v oices, negative symptoms. Aim for quick recovery and relapse prevention through education CBT, p372 \200\2234. \201\201Enlist the family \200\231s support Address carers issues ( embarrassment, self-blame, and shame are prevalent).307 Social support: It is possible that particular social circumstances may result in alterations in dopamine that make relapse mo re likely. Addressing issues with housing, employment, sup- port groups, bene \201 ts and social skills training are all just as important as being concordant with medication. After care: Co-ordinate via an allocated key-worker and a multidisciplinary team (to look at biol ogical, psychological, social and risk issues). It is performed through the Care Program Ap proach (CPA). Family therapy may have a role.308 If concordance with medication is an issue depots are useful, risperidone is now available as a long-acting inject- able form (so les s EP SEs compared to the older \200\230typical \200\231 depot preparations). \201\201 \200\234I don \200\231t want to go on with the tablets \200\235 Relapse is not always a disaster, and drug SE can be bad. Respect his decision, unless sectioning is needed. His li fe may become more meaningful. We tend to be over-impressed by +ve symp- toms (eg hallucina tions) which respond better to drugs than \200\223ve symptoms.309 361 y r t a i h c y s P Substance and behavioral addictions Essence \200\234Visiting prostitutes is unful \201 ll ing, empty, terrible but I keep going. \200\235 Epidemiology of drug addiction Cannabis i s commonly used by young peo- ple (33% men and 22% women), ecstasy is the commonest class A drug (9% of men and 4% of women aged 16 \200\22324).310 Heroin users make up 70% of Home Offi ceuk noti \201 ed addicts. For nicotine and alcohol addiction, see p512 & p363. Other drugs: hydrocarbons/glue sniffi ng, barbiturates, opiates, LSD, ecstasy. Causes Individual factors (age, gender, personality, family background) and interact with external factors s uch as surrounding culture, price, availability, setting, advertising.311 Inherited vulnera bility is equally important.312 Suspect drug addiction if: \200 Arrests for larceny, to b uy drugs \200 Odd behav- iour, eg visual hallucinations, elation, mania \200 Unexplaine d nasal discharge (co- caine sniffi ng) \200 The results of injections: marked veins; abs cesses; hepatitis; HIV \200 Repeated requests for analgesics, with only opiates acceptabl e. Clinical presentation313 Acute intoxication: Follows administration of alco- hol or othe r psychoactive substances resulting in disturbances of level of con- sciousness, cognition, perception, aff ect, or behavior. Harmful use: A pattern of psychoactive substance use tha t is causing actual damage to the mental or physical health of the user Dependence syndrome : 3 or more of the following: 1 Strong desire or sense of compulsion to take the substance (craving). 2 Diffi culty in controlling substance use (onset, termination, level of use). 3 A physiological withdrawal state when reducing or ceasing substance use. 4 Tolerance: incr eased doses are required to produce the original eff ect. 5 Progressive neglect of alternat ive pleasures or interests. 6 Persisting use despite clear evidence of harmful consequences . Opiate detoxi \201 cation and methadone maintenance is ideally as part of a regimen in w hich a contract is made with the patient (p339), eg in a special clinic or in primary care, provided the GP has an interest and commitment.rcgp. org.uk Daily observed methadone dosin g is the norm (NB: monthly supplies are not necessarily abused).314 Drugs used: methadone, eg 20 \200\22370mg/12h PO, reducing by 20% every 2 days (caution: there is no reliable form ula for heroin dose equivalence).315 Cocaine use by patients on methadone is a big problem, and is associated with a poorer prognosis. Disul \201 ram has a role here.316 N=67 A non- addictive alternative is lofexidine ( \200 2-noradrenergic agonist like clonidine) \200 \224 eg 0.2mg/6h PO, increased by 0.4 \200\2230.8mg increments/day (max 0.8mg/8h); a 5-day regimen may be better than 10-day ones. SE: drowsiness, BP \200\201, pulse \200\201, dry mo uth, rebound hypertension on withdrawal.317 Buprenorphine is a syn- thetic partial agonist at -opioid receptors. It may be safer then methadone;318 t \211\210 35h. Start at 0.8 \200\2234mg sublingnally per 24h, titrate by 2 \200\2234mg increments (max 32mg/day, mainte nance: 12 \200\22324mg/day reached within 1 \200\2232 weeks). Cau- tions: liver dysfunctio n; intoxication with other drugs (eg CNS depressants). Naltrexone is an opioid antagonist ( blocks euphoria \200\224useful in former addicts to prevent relapse, eg 25mg/24h PO after s uitable opioid-free period). Warn patient of possible withdrawal reactions and monitor pati ent for 4h after 1st dose; monitor LFT. Psychological support: Tailor to speci \201 c need s (residential or outpatient care, in groups or 1-to-1). Counseling, motivational therapy, cognitive therapy (p372), Alcoholics Anonymous, \200\23012 steps program \200\231, family therapy (p386) are all valuable ways to address triggers, motivation to change, and relapse pre- vention. Counsel about HIV & hepatitis C risk, needle exchange, and safe sex. Relapse prevention As strong cravings precede relapse, anti-craving drugs seem to be a promising b ut unvalidated approach. See acamprosate, p363. 362 (See OHCM p374) y r t a h c y s P i Barbiturate withdrawal may cause seizures death; withdraw as an in- patient ( \205\223 o f the previous daily dose as phenobarbital; lower the dose over 2wks). 363 Alcohol-related problems Alcohol causes as much harm as smoking and hypertension. Abuse imp lies that repeated drinking harms a person \200\231s work or social life. Addiction implies : \200 Diffi culty or failure of abstinence \200 Narrowing of drinking repertoire \200 Increased tolerance to alcohol See p513 for prevention Often aware of compulsion to drink \200 Priority is to maintain alcohol intake \200 Swe ats, nausea, or tremor on withdrawal. Ask about tolerance, worry about drinking, \200\230eye opener \200\231 drinks used in the mornings, amnesia from alcohol use, and attempts to cut down. 2 points is TWEAK +ve (?more sensitive than CAGE questions).319,320 Alcohol & organ damage Liver: (normal in 50% of alco holics). Fatty liver: Acute, reversible; hepatitis; 80% progress to cirrhosis (liver failur e in 10%) Cirrhosis: 5yr survival 48% if alcohol intake continues (if it stops, 77%). CNS: Poor memory/cognition; cortical/cerebellar atrophy; retrobulbar neurop- athy; \201 ts; fa lls; accidents; neuropathy; Korsakoff \200\231s/Wernicke \200\231s encephalopathy (OHCM p7 28; \200 urgent parenteral vitamins are needed). Gut: D&V; peptic ulcer; erosions; varices ; pancreatitis. Marrow: Hb \200\201; MCV \200\200. Heart: Arrhythmias; BP \200\200; cardiom yopathy; fewer MIs (?bene \201 t only if \200\20655yrs). Skeleton: Heavy drinking disrupt s calcium metabolism (osteoporosis risk \200\200).321 Sperm: Fertility \200\201; sperm moti lity \200\201 (in 34 precisely analyzed medical students).322 Malignancy: GI & breast. Soci al: Alcohol is related to violent crime and suicide. In medical students, alcohol correlate s with events such as missing study, sexually escapades, \201 sticuff s, etc323 n=194 \200 and \200 students are equally prone to use alcohol at high doses to relieve stress (this carries on into later years).324 Alcohol and drug levels Regular heavy drinking induc es hepatic enzymes; binging inhibits enzymes; it \200\231s probably not a good idea to indu lge in both and hope for the best. Be alert with phenytoin, warfarin, tolbutamide, etc. NB: par- acetamol may cause \200\200N-acetyl-p-benzoquinoneimine (it is hepatotoxic). Withdra wal signs (Delirium tremens) Pulse \200\200; BP \200\201; tremor; \201 ts; visual or tact ile hallucinations, eg of insects crawling under the skin (formication). \201\227: \200 Admit; monitor vital signs (beware BP \200\201). \200 For the 1st 3 days give diazepam ge nerously, eg 10mg/6h PO or PR if vomiting \200\224or IVI during \201 ts; chlordiazepox- i de is an alternative. After a few days, \200\201diazepam (eg 10mg/8h PO from day 4 \200 \2236, then 5mg/12h PO for 2 more days). \200 -blockers, clonidine, carbamazepine, and neu roleptics (if no liver damage) are adjuncts (not advised as monotherapy).325 Treatment Does the patient want to change? If so, be optimistic, and aug- ment his will to do so. Should abstinence or controlled intake be the aim? If the former, remarkable recovery of organs (e g hippocampus) is possible.326 Treat coexisting depression (p336). Refer to specialists. Se lf-help/group ther- apy (Alcoholics Anonymous) help, drugs which produce a nasty reactio n if alcohol is taken (disul \201 ram 200mg/24h PO). Reducing the pleasure that alco- hol brings (and craving on withdrawal) with naltrexone 25 \200\22350mg/24h PO (an opioid recept or antagonist) can halve relapse rates.327 N=111 SE: vomiting, drowsi- ness, dizziness, joi nt pain. CI: hepatitis; liver failure; monitor LFT. Get expert help. Acamprosate (OHCM p445 ) can treble abstinence rates. CI: pregnancy, severe liver failure, creatinine >120 mol/L; SE: D&V, libido \200\200 or \200\201; dose example: 666mg/8h PO if >60kg and <65yrs old. Economic analysis supports its use, at least in some communities.328 Non-drug, physician-b ased brief interventions for problem drinkers: (Edu- cation, counseling, goal-setting + mon itoring of \200 GT in those who have social or physical problems from alcohol, but who do not exhibit full dependency.) 50% of trials show that \200 GT falls in the intervention gr oup, but none show clear improvement in alcohol-related morbidity. More costly regimens far e no better. Homelessness is common; help with housing & rent, problem-solving, commu- nica tion, drink refusal, and goal setting can help this desperate problem.329 y r t a i h c y s P N=448 N=114