5-HT and NE reuptake inhibition. nausea, GI upset, constipation, loss of Venlafaxine (Efexor , Efexor XL plus many other brand names) \200 Half-life: 1 \200 \2232hrs; peak plasma conc. 5hrs (10hrs for metabolite: desmethylvenlafaxine [Pristiqs US license for depression, anxiety, and menopausal symptoms, 2008 \200\224not licensed in UK yet]). Formulations: Indications: Usual dose: if necessary after at least 2wks to max 375mg /day. Severe depression, begin at 150mg/day, increasing by 75mg every few days to max dose 375mg/day. For GAD and social anxiety, 75mg od (increased 2-weekly to max 225mg/day). Advan tages: more rapid onset of action than other antidepressants; available in controlled relea se form allowing od administration. Disadvantages: monitor blood pressure (BP) at doses ove r 200mg; troublesome side- effects; discontinuation effects common. \200 \200 37.5/75mg tabs (MR 75/150mg caps; 75/150/225mg tabs). depression, GAD, social anxiety. depression, 37.5mg bd (or 75mg od of MR form), increased variable pharmacological pro \201 le over dose range; possibly moderate to high doses less well tolerated; need to Duloxetine (Cymbalta , Yentreve ) \200 \200 \200 Half-life: Formulations: Cautions: potential hepatotoxicity (i.e. cases of severe elevation s of liver enzymes or liver injury with a hepatocellular, cholestatic, or mixed pattern hav e been reported); also caution in glaucoma secondary to mydriasis. Indications: incontinenc e. Usual dose: as necessary to max 120mg/day; diabetic neuropathy 60 \200\223120mg/day (div ided doses); stress urinary incontinence 20 \200\22340mg bd. Advantages: May have utility i n treating chronic pain and urinary incontinence. Disadvantages: discontinuation effects co mmon (note: little evidence that doses greater than 60mg/day confer any additional bene \201 t in depression). 8 \200\22317hrs; peak plasma conc. 6hrs. 30/60mg capsules. depression, GAD, diabetic neuropathy, stress urinary depression 60mg od; GAD start with 30mg od, increasing as for venlafaxine, but no controlled release form available. dose-dependent elevations in BP require monitoring; Tetracyclic antidepressants (TeCAs) Mianserin \200 \200 \200 \200 Mode of action: Half-life Formulations: Indications: similar to TCAs, but with less anticholinergic side-effects. 12 \200\22329hrs; peak plasma conc. 1-3hrs. 10/30mg tabs. depression, particularly if sedation required. 07_Semple_Chap07.indd 278 12/10/2012 6:36:13 PM OTHER ANTIDEPRESSANTS 1 279 Common adverse effects: blood dyscrasias more common (esp. elderly \200\224FBC recommended 4-wkly for \201 rst 3mths of treatment, therafter 3 \200\2236-monthly; stop treatment and check FBC if fever, sore throat, stomatitis, or other signs of infection develop), jaundic e, arthritis, arthralgia. Usual dose: single night-time dose, increased gradually as necess ary; usual range 30 \200\22390mg/day. Advantages: cardiotoxicity), sedating (which may be a desirable effect). idiosyncratic adverse effects. Disadvantages: as for TCAs, but less cardiovascular problems, 30 \200\22340mg (elderly 30mg) daily in divided doses or as a better side-effect pro \201 le than some TCAs (e.g. Serotonin antagonist/reuptake inhibitors (SARIs) Trazodone (Molipaxin ) \200 Mode of action: \200 \200 5-HT 5-HT agonism through the active metabolite (m-chlorophenylpiperazine) \200\224antidepr essant effect; 1A/1C/2A antagonism \200\224sedating/anxiolytic, less sexual dysfunction; H \200 Common adverse effects: similar to TCAs (but less anticholinergic and cardiotoxi c); rarely priapism (discontinue immediately: see b p. 942). 3 \200\2237hrs; peak plasma co nc. 0.5 \200\2232hrs. Half-life: 50/100mg caps; 150mg tabs; liquid 50mg/5mL. Formulations: depression (esp. with insomnia), anxiety disorders. Indications: Usual dose: 150mg/day (as divided dose or just at night), increased to 300mg/day (max dose 600mg/day in divided doses \200\224in hospital). For anxiety, start at 75mg/day \200\224max 300mg/day. sedation (may be used in low doses as an adjunct to other Advantages: less sedating antidepressants or to counter sexual dysfunction), safer in epilepsy than TCAs. Disadvantages: may not be tolera ted. 1 antagonism \200\224orthostatic hypotension; 1 antagonism \200\224sedation and weight gain . sedation; orthostatic hypotension; otherwise \200 \200 \200 the higher doses necessary for antidepressant effects 07_Semple_Chap07.indd 279 12/10/2012 6:36:13 PM CHAPTER 7 Depressive illness 280 Other antidepressants 2 Noradrenergic and speci \201 c serotonergic antidepressant (NaSSA) Mirtazepine (Zispin SolTab ) \200 Mode of action: \200 \200 M \200 \200 \200 H \200 Common adverse effects: s edation (greater at lower doses), increased appetite, weight gain. Less common: transaminas e elevation, jaundice, oedema, orthostatic hypotension, tremor, myoclonus, blood dyscrasias (rare agranulocytosis \200\224if a patient develops a sore throat, fever, stomatitis or si gns of infection accompanied by neutropenia, discontinue medication and closely monitor pat ient). Half-life: 20 \200\22340hrs; peak plasma conc. 1 \200\2233hrs. Formulations: 15mg/mL . Indications: Usual dose: (divided dose or just at night). Advantages: upset. Disadvantage s: (may be used to advantage). 2 antagonism \200\224increases 5-HT and NE release (antidepressant) 1 antagonism \200\224or thostatic hypotension 1 antagonism \200\224anticholinergic side-effects 5-HT 5-HT 2A/C antagonism \200\224sedating/anxiolytic, less sexual dysfunction 3 antagonism \200\224r educed nausea/GI upset 1 antagonism \200\224sedation and weight gain \200 15/30/45mg tabs/orodispersible tabs; oral solution \200 depression (with anxiety, agitation, insomnia, weight loss). 15 \200\22330mg nocte, increas ed if necessary to max 45mg/day low toxicity in overdose, less sexual dysfunction and GI weight gain, sedating effects may be lost at higher doses Noradrenaline reuptake inhibitor (NARI) Reboxetine (Edronax ) \200 \200 Mode of action: Common adverse effects: dizziness, tachycardia, sexual dysfunction, dysuria , urinary retention, dry mouth, constipation, hypokalaemia if used long term in the elderly . Half-life: Formulations: Indications: Usual dose: doses (max 12mg/day). Advantages: patie nts with symptoms of fatigue or hypersomnia; may improve social functioning; relatively saf e in overdose. Disadvantages: NE reuptake inhibition. insomnia, sweating, postural hypotension/ \200 \200 \200 13hrs; peak plasma conc. 2hrs. 4mg tabs (scored). depression (particularly with atypical features). 4mg bd, increased after 3 \200\2234 wks t o 10mg/day in divided novel mode of action; alerting effects may be useful for mainly due to adverse effects. 07_Semple_Chap07.indd 280 12/10/2012 6:36:13 PM OTHER ANTIDEPRESSANTS 2 281 Noradrenergic and dopaminergic reuptake inhibitor (NDRI) Bupropion (Zyban ) \200 Mode of action: \200 Common adverse effects: (nausea, vomiting, abdominal pain, constipation), h ypertension (esp. if also using nicotine patches), risk of seizures (0.4%), taste disturban ce. Half-life: plasma conc. 4hrs. Formulations: Indications: depression (with marked psycho motor retardation or hypersomnia), but only licensed in UK for treatment of nicotine depend ence (and possibly withdrawal from other stimulants); may be useful in adult/child ADHD (un licensed). Usual dose: day max single dose 150mg, min 8h between doses (max duration of tre atment for nicotine dependence 7 \200\2239 wks). Advantages: patients with symptoms of fati gue or hypersomnia, may help treat impulse disorders/addictions when used primarily as an a ntidepressant. Disadvantages: (rare, but may be severe). NE and DA reuptake inhibition. agitation/insomnia, dry mouth, GI upset 3 \200\22316hrs (12 \200\22338hrs active metabolite hydroxybupropion); peak \200 150mg MR. 150mg od, increased after 6 days to 150mg bd max 300mg/ unusual mode of action, alerting effects may be useful for possible seizure induction, hypersensitivity reactions Melatonin agonist and speci \201 c serotonin antagonist (MaSSA) Agomelatine (Valdoxan ) \200 Mode of action: \200 \200 2C antagonism \200\224may increase NE and DA in frontal corte x. Common adverse effects: nausea, dizziness, headache, somnolence, insomnia, migraine, dia rrhea, constipation, upper abdominal pain, sweating, back pain, fatigue, anxiety, raised se rum transaminases; less commonly: paraesthesia, blurred vision, eczema; rarely: hepatitis, rash, suicidal behavior. Half-life: 1 \200\2232hrs. Formulations: Indications: Usual dose: nocte. Advantages: unusual mode of action, possibly useful if there is signi \201 cant sle ep \200\223wake disturbance, well tolerated: no known discontinuation symptoms, sexual side -effects, weight gain, or cardiac effects. Disadvantages: afterwards (recommended: 6, 12, 2 4 wks). Therapeutic role remains to be established as just launched in UK in 2009. MT 5-HT 1/MT2 melatonin agonism \200\224may promote sleep; 1 \200\2232hrs (no major active metabolites); peak plasma conc. \200 \200 25mg coated tablet. depression (with initial insomnia). 25mg nocte increased if necessary after 2wks to 50mg need to check liver function before starting and 07_Semple_Chap07.indd 281 12/10/2012 6:36:13 PM CHAPTER 7 Depressive illness 282 ECT 1: background Electroconvulsive therapy (ECT) A highly effective (if controversial) tre atment for depression (particularly with psychotic symptoms). May act more rapidly than ant idepressant medication. Advances in brief anesthesia and neuromuscular paralysis, introduct ion of brief pulse ECT machines, and the use of EEG monitoring, have led to improved safety and tolerability. Decline in the use of ECT re \202 ects the in \202 uence of non-eviden ce-based factors, rather than being an indicator of its ef \201 cacy (see Box 7.7). Over t he last 20yrs, there have been active efforts to improve standards of delivery, education, and training. These are set out clearly in recent APA and RCPsych publications.1,2 ECT clin ics in England and Wales, Northern Ireland, and the Republic of Ireland are accredited by E CTAS.3 In Scotland the equivalent body is SEAN.4 Does ECT actually work ? \200 5 found: A recent meta-analysis of all ECT studies in depression \200 \200 \200 \200 ECT vs. all placebo ( ECT vs. sham ECT ( ECT vs. pill placebo ( ECT vs. antidepressants (RC Ts) ( 2.60 \200\2235.32). n = 523) OR 4.77 (95% CI: 2.39 \200\2239.49). n = 245) OR 2.83 (95% CI: 1.30 \200\2236.17). n = 266) OR 11.08 (95% CI 3.10 \200\22339.65). n = 892) OR 3.72 (95% CI Mode of action Controversial therapy needs a sound evidence-base. Presuming ignorance ( \200\230we don \200\231t really know how it works, but it does \200\231) ignores real progress in our understanding of ECT. \200 Rejected theories: \200\230fear \200\231, \200\230regression \200\231, or \200\230punish ment \200\231 have been largely discredited; brain injury theory (see b p. 295); amnestic t heory: ECT has some effects on cognitive function (see b p. 294), but this is not the p mod e of action. Anticonvulsant/altered functional activity theory: ECT acts as a powerful anti convulsant (increases seizure threshold, delta activity, and inhibitory transmitters, e.g. GABA and opioids) causing a reduction in functional activity in speci \201 c brain regions related to the therapeutic response (rCBF/glucose metabolism shows reduction in anterior f rontal regions post-ictally and for weeks to months after, associated with better outcomes and correlating with raised seizure threshold). Antidelirium/restorative sleep theory: (e.g . increased delta activity with greater amplitude and reduced frequency) similar to those s een in normal sleep and correlated with clinical improvement. Whether this is a therapeutic action or an (albeit important) epiphenomenon is not certain. Neurochemical theories: expl anations have been advocated for explaining how ECT works, supporting evidence comes from p re-clinical and animal work. Preliminary human studies support a role for DA and GABA/ glut amate. Neuroendocrine theory: it is proposed that ECT works by correcting a dysregulation o f neuropeptides through diencephalic stimulation. psychoanalytical views of ECT ef \201 cacy incorporating ECT does lead to EEG changes despite the fact that neurochemical 07_Semple_Chap07.indd 282 12/10/2012 6:36:13 PM ECT 1: BACKGROUND 283 Studies have found ECT enhances production and release of several neuropeptides (e.g. TRH, prolactin, corticotropin, cortisol, oxytocin, vasopressin, beta-endorphin and, less consist ently, GH). However, these changes could be non-speci \201 c effects of stress/seizure and not necessarily the therapeutic effect of ECT. Other (speculative): neurogenesis: the anim al model of ECT has been shown to promote neurogenesis in non-human primates; gene transcri ption: the likelihood of remission with ECT in patients with treatment-resistant depression has been associated with two polymorphisms related to dopamine metabolism in the prefronta l cortex; brain derived neurotrophic factor (BDNF): preliminary evidence suggests serum BDN F concentrations increase after ECT. Further reading Shorter E and Healy D (2007) Shock therapy: a history of electroconvulsive treatment in mental illness. Piscataway Township: Rutgers University Press. Box 7.7 ECT: an historical perspective The use of convulsive treatments for psychiatric disorders originated with the clinical obs ervation of apparent antagonism between schizo- phrenia (then dementia praecox) and epileps y. Patients who had a seizure were relieved of their psychotic symptoms and Meduna noted in creased glial cells in the brains of patients with epilepsy compared with reduced numbers i n those with schizophrenia. In 1934, he induced a seizure with an injection of camphor-in-o il in a patient with catatonic schizophrenia, and continued this treatment every 3 days. Af ter the \201 fth seizure the patient was able to talk spontaneously, and began to eat and care for himself for the \201 rst time in 4yrs, making a full recovery with 3 further tr eatments. Chemically-induced convulsive treatments using camphor or metrazol (pentylenetetr azol) became accepted for the treatment of schizophrenia, but had problems. Cerletti and Bi ni introduced the use of \200\230electric shock \200\231 to induce seizures in 1938, a met hod that became the standard. Initially, ECT was unmodi \201 ed (i.e. without anesthetic o r muscle relaxant), but because of frequent injury, curare was \201 rst used as a muscle relaxant in the 1940s followed by succinylcholine in the 1950s. Advances in brief anesthesi a mean the current procedure is much safer and recovery more rapid. Indications have also c hanged, with the major- ity of patients receiving ECT for severe depressive illness, althou gh it is also effective in other conditions (see b p. 284). 1 American Psychiatric Association (2001) The practice of electroconvulsive therapy: recomm endations for treatment, training and privileging, 2nd edn. Washington, DC: APA. 2 Royal Co llege of Psychiatrists (2005) The ECT handbook, 2nd edn. The third report of the Royal Coll ege of Psychiatrists \200\231 Special Committee on ECT (Council Report CR128). London: Roya l College of Psychiatrists. 3 ECTAS is the Royal College of Psychiatrists \200\231 ECT Accr editation Service. M http://www.rcpsych. ac.uk/quality/qualityandaccreditation/ectclinics/e ctas.aspx 4 SEAN is the Scottish ECT Accreditation Network. M http://www.sean.org.uk/ 5 Pag nin D, de Queiroz V, Pini S, et al. (2004) Ef \201 cacy of ECT in depression: a meta-analy tic review. J ECT 20: 13 \200\22320. 07_Semple_Chap07.indd 283 12/10/2012 6:36:13 PM CHAPTER 7 Depressive illness 284 ECT 2: indications, contraindications, and considerations Indications (see Box 7.8) \200 Depressive episode: severe episodes, need for rapid antidepressant response (e.g. due to fa ilure to eat or drink in depressive stupor; high suicide risk), failure of drug treatments, patients who are unable to tolerate side-effects of drug treatment (e.g. puerperal depress ive disorder \200\224see b p. 470), previous history of good response to ECT, patient prefe rence. Other indications: treatment-resistant psychosis and mania (50 \200\22360% effective ), schizoaffective disorder (see b p. 218), catatonia (see b p. 992), neuroleptic malignant syndrome (see b p. 956), neurological crises (e.g. extreme Parkinsonian symptoms: on \200 \223off phenomena), intractable seizure disorders (acts to raise seizure threshold). Contraindications There are no absolute contraindications. Where possible, use of ECT shoul d be limited for patients with cerebral aneu- rysm, recent MI, cardiac arrhythmias, intrace rebral hemorrhage, acute/ impending retinal detachment, phaeochromocytoma, high anesthetic risk, and unstable vascular aneurysm or malformation (see b p. 292). Other considerations \200 Time-limited action: bene \201 t from ECT tends to dissipate a fter a couple of weeks. There is a need for a clear maintenance plan to be in place before the course of ECT \201 nishes. ECT should not be considered the only treatment \200\224ex cept in very rare cases when continuation/ maintenance treatment is indicated (see b p. 292 ). Consent concerning use of capacity legislation/Mental Health Act. Decisions rest on asse ssment of capacity, informal/formal status, active (or advance statement) refusal, potentia l as a life-saving intervention. ECT does cause potential side-effects (see b p. 294) and S ide-effects: the administration of ECT will always be a balance of risk and bene \201 t. O f particular note is the potential to cause cognitive problems (see b p. 294) and this may dictate electrode positioning (see b p. 289). Fig. 7.2. (See Table 7.7 for effects of psych iatric drugs on ECT). (b p. 794): guidelines on ECT vary between legislatures 07_Semple_Chap07.indd 284 12/10/2012 6:36:14 PM INDICATIONS, CONTRAINDICATIONS, AND CONSIDERATIONS 285 Box 7.8 NICE Technology Appraisal 59 Guidance on the use of electroconvulsive therapy (May 2003) ECT is used only to achieve rap id and short-term improvement of severe symptoms after an adequate trial of other treatment options has proven ineffective and/or when the condition is considered to be life- threate ning, in individuals with severe depressive illness, catatonia, pro- longed or severe manic episode The current state of the evidence did not allow the general use of ECT in th e management of schizophrenia to be recommended ECT is not recommended as a maintenan ce therapy in depressive illness because the longer-term bene \201 ts and risks of ECT hav e not been clearly established The decision as to whether ECT is clinically indicated should be based on a documented assessment of the risks and potential bene \201 ts to the individual, including: the risks associ- ated with the anesthetic, contemporaneous comorbi dities, anticipated adverse events, particularly cognitive impairment, and the risks of not having the treatment. 07_Semple_Chap07.indd 285 12/10/2012 6:36:14 PM CHAPTER 7 Depressive illness 286 ECT 3: work-up and administration ECT work-up \200 Ensure full medical history and current medication noted on ECT recording sheet. Also note any relevant \201 ndings from physical examination. Ensure recent routine blood results a vailable (FBC, U&Es, any other relevant investigations). If indicated, arrange pre-ECT CXR and/or ECG. Ensure consent form has been signed. Ensure ECT prescribed correctly. Inform an esthetic team of proposed ECT. Inform ECT service of proposed ECT. Ensure patient is aware of the usual procedure and when treatment is scheduled. \200 \200 \200 \200 \200 \200 Pre-ECT checks \200 \200 Check patient \200\231s identity. Check patient is fasted (for 8hrs) and has emptied their bowels and bladder prior to coming to treatment room. Check patient is not wearing restrict ive clothing and jewelry/ dentures have been removed. Consult ECT record of previous treatm ents (including anesthetic problems). Ensure consent form is signed appropriately. Check no medication that might increase or reduce seizure threshold has been recently given. Check ECT machine is functioning correctly. Ensure dose settings are correct for speci \201 c pa tient. \200 \200 Administration of anesthetic \200 \200 Establish IV access. Attach monitoring (heart rate [HR], BP, EEG, electromyograph [EMG]). V entilate patient with pure oxygen via face mask. Give muscle relaxant, followed by short-ac ting anesthetic. Hyperventilation with oxygen is sometimes used to augment seizure activity . Insert bite-block between patient \200\231s teeth to protect tongue and teeth from jaw cl enching (due to direct stimulation of masseter muscles). \200 \200 Administration of ECT \200 \200 Apply electrodes to scalp (see Fig. 7.2 for positioning). Test for adequate contact between the electrodes and the scalp prior to treatment ( \200\230self-test \200\231 function on t he ECT machine). Administer dose. b p. 290). Monitor length of seizure (see Record dose, se izure duration, and any problems on ECT record (and ensure anesthetic administration also r ecorded). Transfer patient to recovery. \200 \200 07_Semple_Chap07.indd 286 12/10/2012 6:36:14 PM ECT 3: WORK-UP AND ADMINISTRATION 287 Table 7.7 Psychiatric drugs and ECT. Note: Ensure anesthetist is fully informed of all medi cations the patient is currently taking Drug class Notes Considerations Recommendations Lowest dose possible. Do not give immediately before ECT (rule of thumb at least 3hrs pre-E CT for last dose) Avoid if possible. Consider non- BDZ hypnotics. Do not suddenly stop if well established Benzodiazepines May reduce antidepressant ef \201 cacy of ECT. Make seizures less likely Antidepressants May augment antidepressant effect of ECT. Reported prolongation of seizures . Reported tardive seizure Use low initial stimulus (dose titration methods). Problems reported more for SSRIs Do not suddenly stop \200\224need for safe reduction to min. dose. Prophylaxis may necessit ate addition of antidepressant towards end of ECT course (inform ECT team of this) Lithium Reduces seizure threshold. May prolong seizures. May increase post-ictal confusion (case re ports only) Use low initial stimulus (dose titration methods) Not contraindicated during ECT Anticonvulsants Raise seizure threshold Clarify if drug is for treatment of epilepsy or as a mood stabilizer. Higher doses of ECT m ay be necessary If prescribed for epilepsy continue \200\224don \200\231t stop. If a mood stabilizer contin ue initially and only reduce if seizure induction is problematic Antipsychotics All tend to reduce seizure threshold. Concerns about clozapine due to case reports of prolo nged and tardive seizures may be overstated Use low initial stimulus (dose titration methods) Clozapine should be withheld 12hrs before any anesthetic and restarted once fully recovered 07_Semple_Chap07.indd 287 12/10/2012 6:36:14 PM CHAPTER 7 Depressive illness 288 Recovery \200 \200 \200 Ensure that there is an adequate airway. Monitor the patient \200\231s pulse and BP until s table. There should be continuous nursing presence and observation until the patient is ful ly orientated. Maintain IV access until able to leave recovery. Bilateral or unilateral eletrode placement?1 The balance of the evidence points to bilatera l electrode placement being preferable in terms of speed of action and effectiveness. In th e past UECT was associated with substantially less memory impairment commonly associated wi th the old sine wave stimulation in BECT. Local ECT policy may vary, but the usual reasons for using unilateral/bilateral electrode placement are: \200 BECT previous good response without signi \201 cant memory problems to BECT. UECT UECT, wh ere minimizing memory problems is a priority, e.g. cognitive impairment already present. : when speed of response is a priority, previous failure of UECT, : speed of response less important, previous good response to 1 Kellner CH, Knapp R, Husain MM, et al. (2010) Bifrontal, bitemperal and right unilateral electrode placement in ECT: randomized trial. Br J Psychiatry 196: 226 \200\22334. 07_Semple_Chap07.indd 288 12/10/2012 6:36:14 PM ECT 3: WORK-UP AND ADMINISTRATION 289 Fig. 7.2 ECT Electrode placement. Bilateral or bitemporal placement Unilateral placement Electrodes positioned on the same point on both sides Non-dominant hemisphere 4cm Midpoint Bilateral ECT (BECT) head. This positioning is also referred to as bitemporal ECT or bi-fro ntotemporal ECT. The center of the electrode on the left (L) and the right (R1) should be 4 cm above, and perpendicular to, the midpoint of a line between the lateral angle of the eye and the external auditory meatus. Unilateral ECT (UECT) \200\230non-dominant \200\231 hem isphere (which is usually the right-hand side). The \201 rst electrode (R1) is in the sam e position as before, but the second electrode (R2) is applied over the parietal surface of the scalp. The exact position on the parietal arc is not crucial; the aims are to maximize the distance between the electrodes to reduce shunting of electrical current and to choose a site on the arc where the electrode can be applied \201 rmly and \202 at against the scalp. The position illustrated in the \201 gure is also known as the \200\230temporo- parietal \200\231 or \200\230d \200\231Elia \200\231 positioning. : one electrode is applied to each side of the : the electrodes are applied to the same 07_Semple_Chap07.indd 289 12/10/2012 6:36:14 PM CHAPTER 7 Depressive illness 290 ECT 4: notes on treatment 2 Ensure you have had adequate training and supervision before ad min- istering ECT.1 Energy dosing Because the higher the stimulus used, the greater the likelihood of tran- sie nt cognitive disturbance, and because once the current is above seizure threshold, further increases only contribute to post-ECT confusion, there are a number of dosing strategies us ed. Local policy and the type of ECT machine used will dictate which method is preferred. F or example: \200 Dose titration: the most accurate method, delivering the minimum stimulus necessary to prod uce an adequate seizure, and therefore to be preferred. Treatment begins with a low stimulu s, with the dose increased gradually until an adequate seizure is induced. Once the approxi mate seizure threshold is known, the next treatment dose is increased to about 50 \200\2231 00% (for BECT) or 100 \200\223200% (for UECT \200\224some protocols 500 \200\223800%) above the threshold. The dose is only increased further if later treatments are sub-therapeutic, and the amount of dose increase will be governed by local policy. Age dosing: selection of a predetermined dose calculated on the basis of the patient \200\231s age (and the ECT mac hine used). The main advantage is that this is a less complex regime. However, there is the possibility of \200\230overdosing \200\231 (i.e. inducing excessive cognitive side-effect s) because seizure threshold is not determined. As ECT itself raises the seizure threshold, the dose is likely to rise by an average of 80% over the length of a treatment course. Higher (or lower) doses will also be needed when th e patient is taking drugs that raise (or lower) the seizure threshold (see b p. 287, Table 7.7). Effective treatment When a subtherapeutic treatment is judged to have occurred, the treat- ment is repeated at different energy settings (see Energy dosing). \200 EEG monitoring phases (see Fig. 7.3). Presence of these features (RCPsych ECT Handbook \200\230new \200\231 [2005] criteria), no matter how short the seizure activity, is deemed to constitute a therapeutic treatment. Usually the ictal EEG activity lasts 25 \200\223130s (motor seizure 720% less). Timing of convulsion: reliable measure of length of observable motor seizure is used, with an effective treatment de \201 ned as a motor seizure lasting at least 15s from end of ECT dose to end of observable motor activity (RCPsych ECT Handbook \200\230old \200\231 [1995] criteria: 15+s visible motor seizure or 25+s on EEG). Cuff te chnique: forearm or leg from the effects of muscle relaxant, by in \202 ation of a BP cuff to above systolic pressure. As the isolated limb does not become paralyzed, the motor seiz ure can be more easily observed. : the gold standard with an ictal EEG having typical where EEG monitoring is not used, the less often under-used technique involving isolation of a 07_Semple_Chap07.indd 290 12/10/2012 6:36:14 PM 0 7 _ S e m p l e _ C h a p 0 7 . i n d d 2 9 1 E C T 4 : N O T E S O N T R E A T M E N T Fig. 7.3 EEG monitoring of ECT. \200\230Real world \200\231 examples of EEG traces for: (A ) a short \200\230therapeutic \200\231 seizure (20s visual and 22s EEG) and (B) a subthres hold \200\230non-therapeutic \200\231 stimulation. In example (A) typical features are see n: 1. End of electrical stimulation; 2. Latent phase \200\224low voltage polyspike activity (no visible convulsion); 3. Increasing amplitude of polyspike activity and slowing of freq uency (associated with clonic phase of convulsion); 4. Classic 3Hz \200\230spike and wave \200\231 (delta) activity; 5. Gradual loss of 3Hz pattern; 6. Endpoint with lower amplitude and fre- quency than baseline ( \200\230post-ictal suppression \200\231). 1 1 www.rcpsych.ac.uk/pdf/ECT%20competencies%20for%20web.pdf 2 / 1 0 2 9 1 / 2 0 1 2 6 : 3 6 : 1 4 P M CHAPTER 7 Depressive illness 292 ECT 5: further notes on treatment Other physiological effects of ECT \200 Musculoskeletal \200\224direct stimulation: supraphysiological bite (not blocked by relaxants; may cause d ental injury; bite block essential); generalized (tonic \200\223clonic) seizure \200\224ris k of fractures (vertebral, long-bone, avulsion). Cardiovascular requirements due to seizure \200\224increased CBF; increase cerebral blood volume; raised ICP. Autonomic effects: incr eased vagal tone \200\224 bradycardia, risk of asystole/AF, salivation; adrenaline release (peak during seizure, resolve over 10 \200\22320mins) \200\224tachycardia, hypertension (po st-ECT monitoring essential). Neuroendocrine may lead to insulin resistance (closely monito r diabetic patients). Other: increased intra-gastric pressure \200\224possible risk of aspi ration (appropriate pre-ECT fasting/premed). Raised intraocular pressure (risk in narrow an gle glaucoma, recent ophthalmic surgery). tonic contraction \200\224opisthotonus, (cf. b p. 284): cerebrovascular: increased metabolic (see b p. 282): increase in ACTH, cortisol, glucagon A course of ECT \200 Rarely will a single treatment be effective to relieve the underlying disorder (but this do es occasionally occur). ECT is usually given twice a week, sometimes reducing to once a wee k once symptoms begin to respond. This limits cognitive problems, and there is no evidence that treatments of greater frequency enhance treatment response. Treatment of depression us ually consists of 6 \200\22312 treatments; treatment-resistant psychosis and mania up to (o r sometimes more than) 20 treatments; and catatonia usually resolves in 3 \200\2235 treatme nts. Continuation or maintenance ECT1 Continuation ECT (C-ECT) Refers to the provision of additi onal treatments during the 6-mth period after remission for the primary purpose of preventi ng relapse. Maintenance ECT (M-ECT) Refers to the prophylactic use of ECT for periods longer than 6mths past the index episode for the purposes of mitigating recurrence. b p. 285, Box \200 Alt hough not recommended in NICE guidelines (see 7.8), the most recent RCPsych ECT Handbook (2 005) accepts the lack of evidence-base but recognizes there are likely to be some patients in the UK who will be prescribed continuation ECT and recommends the guidelines of the APA (2001): \200 \200 \200 \200 there is clear evidence of a previous good response to ECT; evidence for resistance or into lerance to pharmacotherapy; the patient is able to provide informed consent; evidence that the patient \200\231s cognitive function and physical condition do not preclude the ongoing administration of ECT; 07_Semple_Chap07.indd 292 12/10/2012 6:36:15 PM ECT 5: FURTHER NOTES ON TREATMENT 293 the patient \200\231s attitude, circumstances, and level of social support are conducive to ensuring treatment compliance and safety after treatment. There is no speci \201 c or universally supported treatment schedule for C-ECT; however, a fter completing a course of conventional bi-weekly ECT, a common strategy is: weekly for 1m th; fortnightly for 1mth; monthly for up to 6mths after remission. Only in exceptional circ umstances should M-ECT (i.e. > 6mths after remission) be considered as a treatment option, in close consultation with the patient, and a formal review by another consultant, preferab ly with speci \201 c ECT experience. Usually patients are aware of how effective ECT has b een for them and a collaborative approach can be established (balancing frequency of ECT ag ainst return of symptoms and side-effects, esp. memory problems). Outpatient ECT ECT is given to outpatients in exceptional circumstances only: \200 \200 \200 \200 Mild to moderate illness as de \201 ned by a psychiatrist (e.g. CGI 2 \200\2234). Availabi lity of 24hr supervision to ensure safety and observation. The patient should not have acti ve thoughts of suicide. Regular (weekly) assessment by the consultant (or deputy). ECT in pregnancy \200 \200 ECT may be the preferred treatment choice due to its rapid action. ECT in the second or thi rd trimesters may present more technical dif \201 culties for the anesthetist as the risk of aspiration of stomach contents increases. The patient \200\231s obstetrician and the ane sthetist should be involved before a decision is taken to proceed to treatment. Preparation for ECT should be as per routine with the addition of any instructions from the anesthetis t, for example the administration of antacids on the morning of treatment. Any concerns sho uld be reported urgently to the obstetrician. ECT in children and adolescents An exceptionally rare circumstance \200\224hence, special p rovisions apply: \200 The Royal College of Psychiatrists recommends that for those under 16yrs two further opinio ns are sought in addition to the treating consultant: one from a child and adolescent psych iatrist, and one from another psychiatrist from a different clinical unit. Adolescents aged 16 \200\22318 are able to consent and refuse treatment in the same way as an adult, but pa rental approval is advised. In Scotland those under 16 can consent if they understand the p rocess but again parental approval is advised. For compulsory treatment it should be noted that the provisions of legislation governing ECT have no lower age limit. 1 Trevino BA, McClintock SM, and Husain MM (2010) A review of Continuation Eloctroconvulsiv e Therapy: application, safety, and ef \201 cacy. Journal of ECT 26: 186 \200\22395. 07_Semple_Chap07.indd 293 12/10/2012 6:36:15 PM CHAPTER 7 Depressive illness 294 ECT 6: side-effects and other speci \201 c problems Side-effects \200 Early: retrograde amnesia \200\224usually resolves completely (64%), headache (48% \200\224 if recurrent, use simple analgesia), temporary confusion (10 \200\22327%, nausea/vomiting ( 9%), clumsiness (5%), muscular aches. Late: Mortality: no greater than for general anesthes ia in minor surgery (2:100 000) \200\224usually due to cardiac complications in patients wi th known cardiac disease (hence need for close monitoring). some loss of short-term memory see ECT and memory loss. \200 loss of long-term memory (rare \200\224see ECT and memory loss). Speci \201 c problems \200 Persistent ineffective seizures: threshold, consider use of IV caffeine or theophylline. Pr olonged seizures repeated every 30s until seizure stops (alternative \200\224midazolam). Lo wer energy dosing for next treatment. Post-seizure confusion: ensure safety of patient, if necessary consider sedation (e.g. diazemuls/ midazolam). If a recurrent problem, use a low dose of a BDZ prophylactically during recovery, immediately after ECT. check use of drugs that may raise seizure (i.e. over 150 \200\223180s): administer IV diazemuls (5mg) reassurance, nurse in a calm environment, ECT and memory loss \200 Research has focused on retrograde amnesia because of (highly publicized) claims that ECT c auses more enduring de \201 cits in past memories (esp. autobiographical) than new memorie s. These studies show that the period closest to receiving ECT is least well remembered and can be permanently lost. Recent systematic reviews of the evidence for loss of past memori es highlight the dif \201 culties in interpreting the literature, e.g. unknown sensitivity of autobiographical memory measures, need for premorbid measures of cognitive status. Neve rtheless, they \201 nd: \200 \200 Speci \201 c recommendations to minimize memory lo ss include: use of right UECT; brief pulse rather than sine wave ECT; dose titration; limit ed number and frequency of ECT sessions. 1 autobiographical memory loss does occur; it is related to how ECT is administered. Does ECT damage the brain? \200 Psychiatrists \200\224such as Peter Breggin, author of and \200\230Brain-Disabling Treatme nts in Psychiatry \200\231 (2007) \200\224have been very vocal opponents of ECT, believing of \201 cial reports have deliberately ignored evidence of negative effects. Even proponen ts of ECT in early writings suggested they believed that a degree of cerebral damage (akin to a concussion) was necessary for ECT to work \200\224the rejected brain injury theory. \200\230Toxic Psychiatry \200\231 (1993) 07_Semple_Chap07.indd 294 12/10/2012 6:36:16 PM ECT 6: SIDE-EFFECTS AND OTHER SPECIFIC PROBLEMS 295 Strong evidence against ECT causing damage comes from a primate study comparing ECT, MCT, o r anesthesia alone which reports no histological lesions after 6wks of daily treatment.2 Th ere are few post-mortem reports, but one study found no histopathological evidence of brain injury in the brain of a 92-year-old lady with major depression who had received 91 sessio ns of ECT during the last 22yrs of her life.3 Most mental health associations and colleges including the APA and RCPsych have concluded there is no evidence that ECT causes structura l brain damage (see Box 7.9). Box 7.9 Structural brain damage from ECT \200\230Prospective CT and MRI studies show no evidence of ECT-induced structural changes. Some early human autopsy case reports from the unmodi \201 ed ECT era reported cerebrovas cular lesions that were due to agonal changes or undiagnosed disease. In animal ECS studies that used a stimulus intensity and frequency comparable to human ECT, no neuronal loss was seen when appropriate control animals, blind ratings, and perfusion \201 xation techniqu es were employed. Controlled studies using quantitative cell counts have failed to show neu ronal loss even after prolonged courses of ECS. Several well-controlled studies have demons trated that neuronal loss occurs only after 1.5 to 2 hours of continuous seizure activity i n primates, and adequate muscle paralysis and oxygenation further delay these changes. Thes e conditions are not approached during ECT. \200\231