Underlying physical disorder. Withdrawal from drugs of abuse/alcohol. Mania/hypomania (timi ng of onset and symptoms such as dizziness and paraesthesia strongly suggest \200\230disco ntinuation mania \200\231). Management \200 Tapering antidepressant is recommended to reduce the risk of developing discontinuation syn drome (use of liquid preparations may be helpful in allowing greater \202 exibility). How ever, guidelines on the optimum rates of dose reduction are at best empirical (see b p. 268 ) and a cautious approach is advised (over a 4-wk period if duration of treatment \211 8wk s). If mild \200\223moderate and short-lived, symptoms can generally be tolerated by the pa tient, allowing for successful discontinuation of antidepressant. If severe, reintroduction of the original antidepressant rapidly resolves the symptoms. However, the syndrome may re cur in up to 75% of patients when the same antidepressant is later discontinued. Awareness of risk factors and symptoms of discontinuation syndrome, and education of patients prior t o stopping or tapering an antidepressant, should prevent unnecessary and expensive medical investigations. Some symptoms of moderate severity can be treated symptomatically (e.g. hyp notic for insomnia, anti-muscarinic agents for cholinergic rebound following TCA discontinu ation). For SSRI and SNRI discontinuation symptoms another option is to switch to \202 uo xetine (due to its long elimination half-life). If previous history of severe discontinuati on symptoms and poor adherence to treatment, choice of antidepressant with low propensity t o cause discontinuation symptoms (e.g. \202 uoxetine) should be considered. 1 The term \200\230discontinuation \200\231 is usually preferred to \200\230withdrawal \200\231 since the latter implies depend- ence and there is no evidence antidepressants hav e a signi \201 cant dependence liability according to internationally accepted criteria. 2 Haddad PM and Anderson IM (2007) Recognizing and managing antidepressant discontinuation s ymptoms. Adv Psychiat Treat 13: 447 \200\22357. 23_Semple_Chap23.indd 965 12/7/2012 5:12:51 PM CHAPTER 23 Therapeutic issues 966 Hyponatraemia and antidepressants Essence Low serum sodium (Na+<135mmol/L) is a rare, idiosyncratic side-effect of all antide pressants which may have serious consequences if undiagnosed. It is probably not dose-relat ed and its onset usually occurs within the \201 rst month of treatment. Etiology Incompletely understood, but probably due to the syndrome of inap- propriate secre tion of anti-diuretic hormone (SIADH) with resultant euvolaemic hypotonic hyponatraemia. It has been postulated serotonin may be involved in the regulation of ADH release. Risk factors Previous SIADH, history of hyponatraemia; low BMI, female gender, age >80yrs; physical co-morbidity: diabetes mellitus, hypertension, head injury, hypothyroidism, impair ed renal function, COAD; other medications (e.g. thiazides > loop diuretics, chemotherapy, NSAIDs, carbamazepine). Antidepressants \200 Highest risk (>1% incidence) sertraline. Medium risk (0.5 \200\2231% incidence) dosulepine, doxepine, imipramine, lofepramine, moclobemide, paroxetine, venlafaxine. Lowest risk trany lcypromine, mirtazepine, reboxetine. : citalopram, escitalopram, \202 uoxetine, : amitriptyline, clomipramine, (<0.5% incidence): nortriptyline, trazodone, phenelzine, Clinical features Depend upon the severity, duration, and rate of change in serum sodium. M ay be asymptomatic, or display symptoms and signs ranging from nausea, muscle cramps/weakne ss, malaise to hypertension, lethargy, confusion, and, if severe, seizures and coma. Investigations Check renal, hepatic, cardiac, thyroid, adrenal function; volume status; ser um lipids and protein (to exclude pseudohyponatraemia); serum glu- cose (raised in hyperton ic hyponatraemia); urine osmolality (>100mOsm/L indicates impaired free water excretion); s erum osmolality; urinary sodium concentration (usually >20 \200\22340mmol/L with SIADH). Differential diagnosis \200 Psychogenic polydipsia \200 Severe malnutrition. \200 Ant ipsychotic-induced hyperlipidaemia/hyperglycaemia). ; alcoholism. Cirrhosis Nephrotic syndr ome Malignancy, . (water intoxication, SIADH, severe \200 \200 , heart failure. e.g. lung small-cell, pancreas, prostate, lymphoma. 23_Semple_Chap23.indd 966 12/7/2012 5:12:51 PM HYPONATRAEMIA AND ANTIDEPRESSANTS 967 CNS disorders, subdural hemorrhage, head injury, Guillain \200\223Barr , vasculitis. Respi ratory disorders, Endocrine/metabolic hypoadrenalism, pituitary insuf \201 ciency, porphyr ia. Drugs, carbamazepine, NSAIDs, MDMA. e.g. meningoencephalitis, abscess, stroke, subarachnoid/ \200 e.g. TB, pneumonia, abscess, aspergillosis. disease, e.g. severe hypothyroidism, e.g. opiates, chlorpropramide, cytotoxic agents, diuretics, Management Prevention Baseline U&Es prior to commencing antidepressant, with moni- toring f or those at high risk (at 2 and 4wks, then every 3mths). Treatment \200 + is <125mmol/L: refer to specialist medical care and If serum Na withdraw offending agent immediately. If serum Na >135mmol/L. Consider a lower risk antidepressant (mirtazepine appears to have the lowest risk) or, if treatment urgent, ECT may be an option. Consider \202 uid restriction and/or careful use of demeclocycline under specialist advice. If necessary, rechallenge may be possible without recurrence (low dose, gradual increase, close monitoring). + is >125mmol/L: continue to monitor U&Es daily until 23_Semple_Chap23.indd 967 12/7/2012 5:12:51 PM CHAPTER 23 Therapeutic issues 968 Prescribing in pregnancy Data is limited (and often con \202 icting) regarding the safety of psychotropic drugs in pregnancy. There have been reports that psychotropics may be assoc iated with an increased risk of birth defects or neonatal adverse events. However, also unt reated mental illness during pregnancy is an independent risk factor for major congenital m alformations (MCMs) and obstetric complications (see Box 23.11 for guidance). Antipsychotics \200 Based on the available evidence no de \201 nitive association has been found between in ut ero antipsychotic exposure and an increased rate of MCMs and abnormal postnatal development . FGAs are usually considered to have minimal teratogenic potential. For SGAs, most evidenc e is with olanzapine and clozapine (increased rate of gestational diabetes, but no increase d risk of MCMs). Depot formulations and anticholinergic drugs should be avoided. \200 Antidepressants \200 Untreated affective illness in pregnant women may be associated with an increased risk of p re-term delivery, low birth weight, and poorer long-term developmental outcomes. TCAs and S SRIs do not seem to be major teratogens but can cause neonatal withdrawals (agitation, irri tability) if used in 3rd trimester. Among TCAs, nortriptyline is recommended since it is le ss anticholinergic and hypotensive than amitriptyline and imipramine. SSRIs (most experienc e is with \202 uoxetine; less safe is paroxetine) may be associated with low birth weight , spontaneous abortion and, if used in 3rd trimester, neonatal pulmonary hypertension. MAOI s and other antidepressants should be avoided. Anxiolytics \200 Neonatal respiratory depression, hypothermia, hypotonia ( \200\230 \202 oppy baby syndrome \200\231) and withdrawal syndromes may occur when benzodiazepines (BDZs) are used close to delivery. High doses and use in the 1st trimester increase the teratogenic risk. There may be an association between 1st trimester exposure to BDZs (esp. diazepam) and an increased risk of facial clefts. Short-term use and minimum effective dose are recommended if BDZs ar e necessary. Promethazine is often preferred. NICE advises the use of low-dose chlorpromazi ne and amitriptyline. \200 Mood stabilizers \200 All commonly used mood stabilizers are teratogenic and, where possible, should be avoided, at least in the \201 rst trimester. Lithium has been associated with an increased risk (1 :1000) of Epstein \200\231s anomaly (downward displacement of the tricuspid valve into the right ventricle) and detailed ultrasound/fetal echocardiography is indicated at 16 \200\223 18wks. 23_Semple_Chap23.indd 968 12/7/2012 5:12:51 PM PRESCRIBING IN PREGNANCY 969 Relapse rates on discontinuation (50% within 2 \200\22310wks) generally regarded to preclud e stopping lithium therapy in pregnancy. Serum monitoring, dosage adjustment, and ensuring adequate hydration are essential (particularly after delivery). Neonatal problems include \200\230 \202 oppy baby syndrome \200\231, non-toxic goiter, hypothyroidism, nephrogenic d iabetes insipidus, and cardiac arrhythmias. Valproate with neural tube defects (hence, folic acid supplementation is recommended for wo men of child-bearing age, although evidence for bene \201 t is inconclusive). Valproate ha s also been associated with increased risk of long-term cognitive de \201 cits and craniof acial, cardiac, or limb defects. \200 , and to a lesser extent carbamazepine, are associated Detailed ultrasonography should be carried out at 16 \200\22318wks, and maternal serum A-fe toprotein (AFT) levels measured. There is also an increased risk of neonatal hemorrhage, an d vitamin K should be given to mothers in the last month of gestation (and to neonates at b irth). may be associated with increased rate of cleft palate. Lamotrigine Box 23.11 Guiding principles For all women of child-bearing age \200 \200 \200 \200 Always consider (and ask about) the possibility of pregnancy. Pregnancy test recommended be fore starting any teratogenic drug. Counsel the patient about the necessity of adequate con traception. Advise further consultation if pregnancy is planned. For a planned conception \200 Discuss risks/bene \201 ts of discontinuation/continuation of medication (e.g. relapse vs. teratogenicity, possible time it may take to conceive, no decision is risk-free). Avoidanc e of all drugs during the \201 rst trimester (max teratogenic potential is between wks 2 \200\2239) is ideal, but often not achievable. In pregnancy \200 Consider switching to a lower risk drug if possible, use the lowest viable dose, avoid poly pharmacy, and monitor closely. Pregnancy may alter the pharmacokinetics of drugs, hence dos ages may need to be adjusted (e.g. lithium). Gradual withdrawal of some compounds (e.g. BDZ s, TCAs, SSRIs) in the weeks prior to delivery may help avoid \200\230withdrawal \200\231 effects in the newborn baby. Unexpected pregnancy \200 If after week nine, no urgent decision needs to be made as major risk has passed. Consider reducing dose if possible and prescribe nutritional supplements (e.g. folic acid). Do not s top lithium abruptly and use caution with some SSRIs and anticonvulsants. 23_Semple_Chap23.indd 969 12/7/2012 5:12:52 PM CHAPTER 23 Therapeutic issues 970 Prescribing in lactation 1 Absolute contraindications Psychotropic drugs should be avoided if the infant is premature or suffers from renal, hepatic, cardiac, or neurological disorde rs. General points \200 All psychotropic medication should be regarded as passing into breast milk (to a greater or lesser degree). The bene \201 ts of breastfeeding to the mother and the infant must be ca refully weighed against the risks of neonatal exposure to drugs. Of the limited studies exa mining this problem, the general \201 ndings are that levels of most psychotropic drugs i n breast milk are relatively low, and infant serum levels (ILs) may be undetectable. Althou gh infant exposure may be relatively low from breast milk (much lower than in utero exposur e if mother was taking medication during pregnancy), there is a risk of both withdrawal sym ptoms and adverse effects on development. Evidence may be lacking for be exercised. Monitor ing of the infant should include biochemical (renal and liver function tests) and behaviora l measures, with the involvement of a pediatrician to ensure development is within normal p arameters. speci \201 c risks, nonetheless, caution should Choice of medication in nursing mothers \200 \200 Where possible, consider non-pharmacological treatments. If medication is necessary, the lo west effective therapeutic dose should be used and polypharmacy should be avoided. Unless o therwise contraindicated, consider continuing with the psychotropic used during pregnancy i n order to minimize any withdrawal effects in the newborn. Avoid the use of drugs which are sedating and with long half-lives. Antipsychotics \200 Limited data preclude any conclusive prediction on the long-term safety of the available an tipsychotics in lactation. Among FGAs, most evidence is with haloperidol and chlorpromazine and has not shown any clear adverse infant effects. A few case reports indicate low breast milk levels with risperidone, quetiapine, and olanzapine. There is one case report of card iomegaly, jaundice, and sedation with olanzapine but this \201 nding may be spurious. Clo zapine should not be used as there is a risk of agranulocytosis and seizures in the infant. Antidepressants \200 Available evidence is reassuring with regard to the safety of SSRI use in lactating women, with few reports of adverse effects on exposed infants. 23_Semple_Chap23.indd 970 12/7/2012 5:12:52 PM PRESCRIBING IN LACTATION 971 Low ILs have been found with all SSRIs but higher concentrations have been reported with \202 uoxetine and citalopram, which should therefore be used with caution. Sertraline and p aroxetine should be considered \201 rst-line since they are usually associated with undet ectable ILs. Low ILs and no adverse effects in the nursing infant are also reported with TC As, with imipramine and nortriptyline being recommended as drugs of choice. Limited data is available on other antidepressants. Anxiolytics \200 Benzodiazepines (BDZs) are excreted in breast milk and have lower infant milk/plasma ratios than other psychotropic medications. Adverse effects such as sedation, lethargy, and weigh t loss have been reported with the use of BDZs. BDZs with a short half-life such as lorazep am and oxazepam are preferable to longer acting ones (e.g. diazepam). Mood stabilizers \200 Valproate and carbamazepine are regarded as compatible with breastfeeding. However, some ad verse effects have been noted, hence close monitoring of the infant is advised. Previous ca se reports found high ILs and adverse infant effects (such as cyanosis, hypotonia, heart mu rmur, lethargy) being associated with lithium. However, recent data have shown no serious a dverse event and relatively low ILs. Infants may be more susceptible to dehydration and lit hium toxicity owing to immature renal function. In the light of the recent \201 ndings, t here is no absolute contraindication to the use of lithium in lactating women but caution a nd careful monitoring are recommended. Lamotrigine is not recommended due to theoretical ri sk of life- threatening Stevens \200\223Johnson syndrome. Strategies to minimize infant exposure \200 Breastfeeding should be avoided at the time when serum levels in the mother are likely to b e at their peak (check drug information for these values). If possible, medication should b e given as a single dose before the infant \200\231s longest sleep period. Breastfeeding sh ould occur immediately dose. Alternatively, breast milk may be expressed when serum levels are at their lowest. before taking the next due 23_Semple_Chap23.indd 971 12/7/2012 5:12:52 PM CHAPTER 23 Therapeutic issues 972 Prescribing for patients with cardiovascular disease General points In considering a suitab le psychotropic drug the main issues revolve around the propensity of that drug to interact with other medications the patient may be taking, to affect blood pressure, or lead to car diac conduction problems (see Box 23.12). Due to the unpredictability of drug interactions, polypharmacy is best avoided. Speci \201 c contraindications BDZs and clomethiazole in pulmonary insuf \201 ciency; dis ul \201 ram and lithium in heart failure or sick sinus syndrome; lofexidine in post-MI pat ients. Pimozide is best avoided in most conditions. Myocardial infarction \200 Antidepressants: SSRIs (sertraline is drug of choice), rather than TCAs (but avoiding \202 uvoxamine and citalopram/escitalopram). If sedation required consider use of a small d ose of trazodone at night. Antipsychotics: generally more hypotensive than butyrophenones; clozapine should be used with caution in the 1st year post-MI; of the newer antipsychotics, olanzapine may offer best risk \200\223bene \201 t balance. best avoided in the \201 rst 2mths; if clinically indicated \200\224 high doses should be avoided; phenothiazines are Heart failure Where possible, hypotensive agents (B-blockers, clozapine, risperidone, TCAs) and drugs causing \202 uid retention (carbamazepine, lithium) should be avoided. Angina/IHD Avoid hypotensive agents and those known to cause tachycardia (phenothiazines, c lozapine, risperidone). Hypertension Avoid agents that may raise blood pressure (MAOIs, low-dose TCAs, phenothiazin es, clozapine, high-dose venlafaxine). Arrhythmias (see Box 23.12) \200 Antidepressants: citalopram/escitalopram). Antipsychotics: sulpiride and olanzapi ne is rec ommended. SSRIs should be \201 rst choice (but not \202 uvoxamine or high doses should be avoided; if essential, use of 23_Semple_Chap23.indd 972 12/7/2012 5:12:52 PM PRESCRIBING FOR PATIENTS WITH CARDIOVASCULAR DISEASE 973 Box 23.12 The QTc question Awareness of QT prolongation, as measured by the corrected QT interval (QTc), has been heig htened because of the potential (but rela- tively rare) risk of fatal arrhythmias (e.g. tor sade de pointes), highlighted recently by the withdrawal of thioridazine as a \201 rst-li ne antipsychotic (and now contraindicated in patients with a history of, or at risk of, arr hythmias) and speci \201 c new cautions regarding high-dose citalopram/ escitalopram. QTc is derived by dividing the QT interval by the square root of the cycle length i.e.: QT \210\222 R R c = QT Normal QTc is 380 \200\223420ms; if prolonged to 450ms \200\224some concern; if >500 \200 \223520ms \200\224 \200\230at risk \200\231. Causes of prolonged QT interval Acute myocardial ischaemia, myocarditis, bradycardia (e.g. AV block), head injury, hypothermia, electrolyte imbalance (K+ i, Ca2+ d, Mg2+ d), congenit al, sotalol, antihistamines, macrolides (e.g. erythromycin), amiodarone, antipsychotics (es p. phenothiazines), antidepressants (esp. TCAs). General advice Good practice dictates use of routine ECG prior to commencement of antipsych otic medication (esp. pimozide, zotepine, thioridazine, and other phenothiazines) or other psychotropics with known cardiac side- effects (e.g. \202 uvoxamine, citalopram/escitalop ram), and regular monitor- ing, particularly when high doses are prescribed. 23_Semple_Chap23.indd 973 12/7/2012 5:12:52 PM CHAPTER 23 Therapeutic issues 974 Prescribing for patients with liver disease General points \200 \200 Almost all psychotropic drugs are metabolized by the liver. Exceptions to this rule include lithium, gabapentin, sulpiride, and amisulpiride, which have minimal (or no) liver metabol ism. Most drugs are highly protein-bound (with the exception of citalopram, escitalopram, s ulpiride, and amisulpiride) and plasma levels may be increased in liver disease. In liver d isease, when using drugs with high \201 rst-pass clearance (e.g. imipramine, amitriptylin e, desipramine, doxepin, haloperidol), initial doses should be low. Where possible, phenoth iazines (e.g. chlorpromazine), hydrazine, and MAOIs (may be hepatotoxic) should be avoided. Avoid drugs that are very sedative and constipating (anticholinergic) due to increased ris k of precipitating hepatic encephalopathy. LFTs can be a poor marker of hepatic metabolic i mpairment; hence always consider the clinical presentation too. Risk factors for drug-induced hepatotoxicity are: older age, alcohol intake, female sex, ob esity, genetic vulnerability, concomitant prescription of enzyme-inducing drugs. Antidepressants \200 \200 Always start with lowest possible dose and titrate slowly. TCAs: dothiepin, and lofepramine (most hepatotoxic). SSRIs: Also increased risk of bleeding with all SSRIs. when clinically necessary, use 30 \200\22350% usual dose. MAOIs: Others: venlafaxine (use 50% of usual dos e), mirtazepine (cautious use), reboxetine (extensively metabolized, very low starting dose ), trazodone (highly protein bound so low starting dose). best evidence for use of imipramine; avoid amitriptyline, some evidence for paroxetine and citalopram; avoid sertraline. \200 Antipsychotics \200 Best evidence for low-dose haloperidol (considered \200\230drug of choice \200\231), with sulpiride a close second (only 5% liver metabolism). Few problems reported for \202 upent hixol/zuclopenthixol. Clozapine dose should be kept low (some evidence of hepatotoxicity). Amisulpiride is predominantly excreted by the kidneys, but there is little literature on it s use in liver disease. For the newer agents recommendations suggest: \200 \200 \200 \200 Aripiprazole should be used cautiously esp. in severe disease. Olanzapine (up to 7.5mg) may be safe (but does induce transaminases). Risperidone doses should be kept low (start 0.5mg bd, max 4mg/day). 23_Semple_Chap23.indd 974 12/7/2012 5:12:52 PM PRESCRIBING FOR PATIENTS WITH LIVER DISEASE 975 \200 Quetiapine is extensively metabolized (hence, start low \200\22425mg). Zotepine should only be used with caution (start 2.5mg bd, max 75mg/day, monitor LFTs weekly for at least 3mths ). Mood stabilizers \200 \200 Lithium is the \200\230drug of choice \200\231, with gabapentin as second choice. Valproat e is with caution in mild \200\223moderate impairment. Caution should also be exercised wit h carbamazepine and lamotrigine, which are contraindicated in severe and acute liver diseas e. contraindicated in severe liver disease, but may be used Anxiolytics \200 Where necessary, use low doses of short-acting BDZs (e.g. lorazepam, oxazepam, temazepam). A low dose of zopiclone 3.75mg can be used with care in moderate hepatic impairment. If chl ormethiazole is to be used, the dose should be reduced to 730%. 23_Semple_Chap23.indd 975 12/7/2012 5:12:52 PM CHAPTER 23 Therapeutic issues 976 Prescribing for patients with renal impairment General points \200 Renal impairment generally leads to accumulation of drugs (or active metabolites) that are predominantly cleared by the kidney. This will lead to higher serum levels, and increased r isk of dose-related side- effects (e.g. postural hypotension, sedation, EPSEs). Hence, all psychotropics should be started at a low (or divided) dose, increased slowly, and carefully monitored (for ef \201 cacy and tolerability). When patients are receiving dialysis, seek speci \201 c advice from manufacturer \200\224dosages should usually be reduced by at lea st 50% and dosing separated in time from dialysis itself. Classi \201 cation of chronic renal failure (CRF) See Box 23.13 for estimation of GFR. CRF may be classi \201 ed as mild (glomerular \201 ltration rate [GFR] 60 \200\22389mL/min) , moderate (GFR 30 \200\22359mL/ min), severe (GFR 15 \200\22329mL/min), or end-stage (GFR <15mL/min). Antidepressants \200 In severe renal failure avoid duloxetine, \202 uoxetine, venlafaxine, and lofepramine (un less the patient is on dialysis). Otherwise cautious use, beginning low and gradually incre asing the dose is advised. No speci \201 c therapeutic dose adjustments are necessary for MAOIs (except for isocarboxazid), RIMAs, mianserin, tryptophan, trazodone, or TCAs. Antipsychotics \200 Lower doses are recommended to avoid dose-related side-effects (particularly with the pheno thiazines, which may be best avoided). Highly anticholinergic agents should be avoided due to risk of urinary retention. Clozapine is contraindicated in severe renal impairment. Avoi d amisulpiride/sulpiride (primarily renally excreted) and use caution with risperidone and zotepine. Some authorities recommend haloperidol, but accumulation is possible, so careful monitoring is still necessary. \200 Mood stabilizers \200 Lithium is relatively contraindicated in renal failure, but its use may often be necessary, and dose reduction (e.g. to 50 \200\22375% for mild \200\223 moderate and 25 \200\22350% f or severe renal failure) with close monitoring of plasma levels is recommended. In dialysis , 600mg \2273/wk (after dialysis) has been shown to maintain therapeutic plasma levels. No speci \201 c problems are reported for valproate or carbamazepine, although in severe ren al failure, serum levels should be monitored. 23_Semple_Chap23.indd 976 12/7/2012 5:12:52 PM PRESCRIBING FOR PATIENTS WITH RENAL IMPAIRMENT 977 Box 23.13 Estimating glomerular \201 ltration rate (GFR) GFR Normal value approx. 125mL/min, is the volume of \202 uid \201 ltered by the glomer uli per minute (mL/min) and can be directly measured by collec- tion of urine over 24hr or estimated in adults in two ways: \200 : Using the Cockcroft and Gault equation: Creatinine clearance (CrCl) CrCl (mL/min) = F(140 \200\223 age [in yrs] \227 ideal body weight [kg])/se- rum creatinine ( mol/L) F = 1.23 (men) and 1.04 (women). CrCl is not accurate in conditions where plasma creatinine is unsta- ble (pregnancy, childr en, diseases raising creatinine plasma level) and in severe renal failure. \200 : Using the Modi \201 cation of Diet in Renal Estimated GFR (eGFR) Disease (MDMR) formula. It gives an eGFR for a 1.73 m2 body surface area (if the body surface area is more or less than 1.73 m2 then eGFR is less accurate). eGFR (mL/min/1.73m2) = 175 \227 ([serum creatin ine ( mol/L)/ 84.4] \200\2231.154) \227 age(yrs) \200\2230.203 \227 0.742 if female \227 1.21 if African American or African Caribbean Online calculator is available at M www.renal.org/eGFRcalc/GFR Note: most current drug dose recommendations are based on the CrCl estimations from Cockroft and Gault. However, the mo st widely used method for estimating GFR is the MDMR equation, as this has proved the most robust and accurate. Gabapentin requires speci \201 c dose adjustments and manufacturer \200\231s recommendatio ns should be sought. Lamotrigine should be used cautiously, particularly in severe renal im pairment. Anxiolytics/hypnotics \200 BDZs (with the exception of chlordiazepoxide) tend to accumulate, with increasing CNS side- effects (particularly sedation) \200\224hence use low doses. Buspirone is contraindicated i n moderate \200\223severe renal failure. B \200 blockers should be started at low dose as they may complicate renal failure by reducing renal blood \202 ow. Zopiclone and zaleplon require no dosage adjustm ent. However, the half-life of zolpidem may be doubled in renal failure. Others \200 \200 \200 Anticholinergics, disul \201 ram Acamprosate Anticholinesterases : use cautiously. : contraindicated if serum creatinine >120 mol/L. : no reported problems. 23_Semple_Chap23.indd 977 12/7/2012 5:12:52 PM CHAPTER 23 Therapeutic issues 978 Prescribing for patients with epilepsy General points In considering a suitable psychotropi c considerations: \200 there are two related The propensity of that drug to interact with other medications the patient may be taking (j ustifying serum monitoring where possible). Risk of lowering seizure threshold and exacerba ting the condition. As these effects appear dose-related, daily dose of any drug should be kept as low as possible. Greater caution is necessary when: Other psychotropics are also be ing given (e.g. regular \200 required \200\231 antipsychotics). Patients may be withdrawi ng from CNS depressants (e.g. BDZs, barbiturates, or alcohol). \200 plus \200\230as Risk factors for psychotropic-induced seizures include: history of epilepsy, old age, polyp harmacy, reduced drug clearance, pre-existing EEG abnormalities, cerebral arteriosclerosis, neurological impairment. Antidepressants \200 All TCAs appear to lower seizure threshold, although there appears to be greater risk with amitriptyline, clomipramine, and dothiepin. Tetracyclics (maprotiline and amoxapine) also a ppear pro-convulsant, as does bupropion. The other antidepressants appear less likely to ca use problems, and a usual \201 rst choice is often an SSRI (may be anticonvulsant at ther apeutic doses). Antipsychotics \200 Greatest risk of seizures is associated with the use of phenothiazines (esp. chlorpromazine ), zotepine, olanzapine, and particularly clozapine. The risk of seizures with clozapine ri ses from 1% (at doses <300mg/ day), to 2.7% (300 \200\223600mg/day), to 4.4% (>600mg/day). EEG changes are seen in up to 75% of people taking clozapine, with 740% showing paroxysmal discharges.1 Because of this risk it is quite common to cover high doses of clozapine with concomitant use of valproate. Hence, greater caution is needed when clozapine is used in in dividuals with epilepsy. Lowest risk is associated with haloperidol (best choice), sulpirid e, zuclopenthixol, amisulpiride, pimozide, quetiapine, and risperidone. Mood stabilizers \200 Lithium does cause seizures in overdose. However, a therapeutic dose has a low pro-convulsi ve effect. If in doubt, anticonvulsants provide useful alternatives. However, clinical ef \201 cacy must be weighed against any potential risks of using lithium. 23_Semple_Chap23.indd 978 12/7/2012 5:12:52 PM PRESCRIBING FOR PATIENTS WITH EPILEPSY 979 Anxiolytics/hypnotics \200 \200 Generally these drugs are Exceptions include buspirone, zolpidem, and there is no evidence that they are epileptogenic. anticonvulsant. B-blockers, although Others \200 \200 \200 Anticholinergics, acamprosate: Disul \201 ram: Anticholinesterases: However, galantamine a ppears safe. no problems reported. caution is recommended. care is needed with donepezil and rivastigmine. 1 Pacia SV and Devinsky O (1994) Clozapine-related seizures: experience with 5,629 patients . Neurology 44: 2247 \200\2239. 23_Semple_Chap23.indd 979 12/7/2012 5:12:53 PM This page intentionally left blank 981 Chapter 24 Dif \201 cult and urgent situations Dealing with psychiatric emergencies 982 What to do if summoned to a crisis situation/negot iation principles 984 Managing suicide attempts in hospital 986 Severe behavioral disturbance 988 Pharmacological approach to severe behavioral disturbance 990 The catatonic patient 992 The manipulative patient 1 994 The manipulative patient 2 996 Iss ues of child protection 998 Patients acting against medical advice 1: guiding principles 10 00 Patients acting against medical advice 2: clinical scenarios 1002 The mental health of d octors 1004 Looking after your own mental health 1006 24_Semple_Chap24.indd 981 12/7/2012 5:42:55 PM CHAPTER 24 Dif \201 cult and urgent situations 982 Dealing with psychiatric emergencies It is a common misconception that there are no real em ergencies in psy- chiatry. The billowing white coat may be gone, but then so is the back-up of the arrest team. Dealing with acute situations can feel like a lonely business, and dou bts about the best management of given situations may prevent you getting that much-needed rest period. As a psychiatrist, you are primarily a doctor, and you should ensure that you are up to dat e with basic resuscitation procedures. Familiarize your- self with the procedures in place for the management of medical emergen- cies in your hospital, as the level of on-site facil ities will vary. There is no substitute for experience, but hopefully some of the guid- ance in the followin g section (and the other pages they refer to) will allow a rational approach to a number of common (and not so common) dif- \201 cult and urgent situations in a psychiatric setting . Keep the following principles in mind: \200\230Primum non nocere \200\231: above all, do no harm \200 Always ensure your own an d other staff \200\231s safety. \200 If necessary facilities or expertise are not availab le, make appropriate arrangements to get the patient to them as soon as possible. Always su spect (and as far as possible exclude) potential organic causes for psychiatric presentatio ns. Remember \200\224patient con \201 dentiality does not override issues of threatened ha rm to themselves or other individuals. Assess \200 Always make the fullest assessment possible \200\224do not fail to ask about important issu es just because you feel a person may not wish to talk about them. Ensure that you have the best quality information available. If other sources of information are available (e.g. pr evious notes, third-party information), use them! Don \200\231t dawdle \200\224if a situati on requires immediate action, act. Consult \200 assume anything. If in doubt, consult a senior colleague. Do not Remember yo u are part of a team, and if there is a dif \201 cult decision to make, do not make it alo ne. Keep contemporaneous records \200 Clearly record your assessment, decisions made ( and reasons), and the names of any other c olleagues involved or consulted. Legally, if it \200\231s not been recorded, it \200\231s n ot been done. 24_Semple_Chap24.indd 982 12/7/2012 5:42:55 PM This page intentionally left blank CHAPTER 24 Dif \201 cult and urgent situations 984 What to do if summoned to a crisis situation/negotiation principles First principles \200 \200 Speak to the staff who originated the call. Obtain as much information as possible about th e situation prior to seeing the patient. Establish what your expected role is. Keep your ow n safety uppermost in your mind (no heroics). \200 General aims \200 Attempt to put the patient at their ease; explain who you are and why you have been asked t o speak to them. Be clear in any questions you need to ask. Elicit useful information. Achi eve a safe, digni \201 ed resolution of the situation. \200 \200 Important communication principles \200 Be conscious of both verbal and non-verbal language. \200 Listen actively \200\224assimilate and understand what is actually being said and interpret the various underlying meanings and messages. Feedback \200\224go back over what the patie nt has said with them to assure them that you understand what they are saying. Empathy \200 \224show you appreciate them sharing their thoughts, feelings, and motives. Content and fee ling \200\224note any difference between what is said verbally and what message is really b eing given. Use checkpoint summaries \200\224brief reviews of the main points discussed, about issues, and any demands. Important suggestions \200 Use open questions to give the patient an opportunity to ventilate what is on their mind (t his may help relieve tension, keep the patient talking, and allow you to assess the mental state). Listen carefully to what the patient is saying. This may provide further clues as t o their actions. It also demonstrates concern for the patient \200\231s problem. Be honest, up front, and sincere \200\224develop a trusting relationship. Be neutral \200\224avoid ap proval or disapproval unless necessary. Orientate the patient to looking for alternative so lutions together, without telling them how to act (unless asked). Try to divert any negativ e train of thought. Check with other team members before making any commitments. If the pol ice have been called, present the reason for their presence realistically, but neutrally. D o not involve family members in negotiations. \200 \200 \200 \200 24_Semple_Chap24.indd 984 12/7/2012 5:42:55 PM CRISIS SITUATION/NEGOTIATION PRINCIPLES 985 Some suggestions for dealing with particular patients The patient responding to paranoid id eas/delusions \200 \200 Avoid prolonged eye contact and do not get too close. The patient \200\231s need to explain may allow you to establish a degree of rapport. Allow them to talk, but try to stay with c oncrete topics. Do not try to argue them out of their delusions \200\224ally yourself with their perspective without sounding insincere (e.g. \200\230What you are saying is that you believe x y z \200\231). Avoid using family members who may be part of t he delusional system. Try to distance yourself from what may have happened in the past (e.g . \200\230I \200\231m sorry that was your experience before maybe this time we could manage things better \200\231). Be aware that your offer of help may well be rejected . \200 The patient with antisocial traits \200 A degree of \202 attery may facilitate discussion of alternative solutions (show you unde rstand their need to communicate, how important their opinions are, your desire to work tog ether to resolve things). Encourage them to talk about what has led up to this situation. T ry to convince them that other ways of achieving their aims will be to their advantage \200 \224keep any negotiation reality-oriented. Focus their attention on you as the means to ach ieve their aims. \200 The patient with borderline traits \200 \200 \200 Provide \200\230understanding \200\231 and \200\230uncritical acceptance \200\231. Help t hem \201 nd a way to sort things out without having \200\230failed again \200\231. Try t o build self-esteem (e.g. \200\230You have done well coping with everything up to now \200\231) Once trust is gained, it may be possible to be more directive. Use the patient \200\231s desire to be accepted (e.g. \200\230I really think it would be best if we \200\231). Bear in mind that often the behavior will be attention-seeking, and it may be wo rth asking: \200\230What is it you feel you need just now? \200\231 Do not be surprised if the patient acts impulsively. \200 The depressed patient \200 \200 Psychomotor retardation may slow response time \200\224be patient. The presence of friends or relatives may worsen their feelings of worthlessness and guilt. Focus on the \200\230he re and now \200\231 \200\224avoid talking abstractly. Acknowledge that they probably cannot imagine a positive future. Be honest and straightforward \200\224once rapport has been est ablished, it may be appropriate to be explicitly directive. Try to postpone the patient \200\231s plans, rather than dismiss them (e.g. \200\230Let \200\231s try this and s ee how you feel in the morning \200\231). Be prepared to repeat reassurances. \200 \200 The patient experiencing acute stress \200 \200 \200 \200 Allow ventilation of feelings. Try to get them to describe events as objectively as possibl e. Have them go back over the options they have ruled out. Review the description of events , and present a more objective, rational perspective. 24_Semple_Chap24.indd 985 12/7/2012 5:42:55 PM CHAPTER 24 Dif \201 cult and urgent situations 986 Managing suicide attempts in hospital Attempted overdose In psychiatric wards, the most lik ely means of attempted self-poisoning involves building up a stock of prescribed medication or bringing into the ward tablets to be taken at a later date (e.g. while out on pass). Of ten patients will volunteer to trusted nursing staff that they have taken an overdose, or s taff will notice the patient appears overtly drowsy and when challenged the patient admits to overdose. \200 