PSY11 Switching and stopping drugs

By the end of this lecture you will be able to: • Understand the impact and limitations of stopping and switching antidepressants • Understand the impact and limitations of using prolonged release antipsychotic drugs • Interpret recommendations for switching between oral and depot formulations • Be aware of the potential reasons for antipsychotic polypharmacy and associated risks [blank_start]OK[blank_end]

Antidepressants: • Sudden stop not recommended due to increased risk of [blank_start]relapse[blank_end] • Slow tapering doesn’t always [blank_start]↓[blank_end] incidence/severity of discontinuation [blank_start]reactions[blank_end] • Some may prefer abrupt stop and [blank_start]shorter[blank_end] • All have the potential to cause withdrawal phenomena if taken [blank_start]>6[blank_end] weeks • Cross [blank_start]tapering[blank_end] preferred but low need if transferring between drugs of the same [blank_start]class[blank_end] (ie can go from one SSRI to another abruptly) • Co-administration of some antidepressants, even when cross-tapering, is absolutely contraindicated for example [blank_start]MAOIs and SSRIs[blank_end]. Follow the Maudsley's guidelines and consider half lives.

Antipsychotics TDM - • Plasma concentration don’t necessarily [blank_start]reflect[blank_end] brain concentration which can be up to 20 times [blank_start]greater[blank_end] • TDM [blank_start]not[blank_end] strictly necessary for all antipsychotics because there are no unequivocal data supporting a relationship between plasma drug concentrations and clinical outcomes or SEs - Exception is [blank_start]clozapine[blank_end]. • After 1-2 years of taking an antipsychotic following a first episode and remaining well, the risk of relapse remains high - up to [blank_start]10-15[blank_end]% risk per month • If withdrawing an antipsychotic after 1 year, the risk of relapse is ~ [blank_start]80[blank_end]% and after 2 years [blank_start]98[blank_end]% • All psychotics cause discontinuation after some time. • [blank_start]Aripiprazole[blank_end] is better for managing long-term CV risk and mortality • Maudsley states ‘if a patient has alreadytried [blank_start]olanzapine and risperidone[blank_end] the benefits of switching rather than staying could be marginal’ • Clozapine, olanzapine worst for [blank_start]weight gain[blank_end] • Chlorpromazine, haloperidol worst for [blank_start]EPSEs[blank_end]

Depot antipsychotics? • Lack of or, partial compliance is a key [blank_start]barrier[blank_end] to the management of psychotic disorders and often a contributing factor to [blank_start]relapse[blank_end] • Non-adherence is [blank_start]common[blank_end] • Optional for patients of Mental Health ([blank_start]compulsory[blank_end] assessment and treatment) Act – 1992 • Disadvantages – impossible to quickly [blank_start]alter[blank_end] dose as a result of drug-induced side effects, depot injections can be [blank_start]painful[blank_end] for up to 10 days leading to negative views • Depots show better [blank_start]correlation[blank_end] between the dose taken and plasma concentrations than oral doses - absorption less [blank_start]variable[blank_end] than oral, no [blank_start]first pass[blank_end] metabolism, compliance better

• Offer a LAIs (Long-acting injections or depots) to those; 1. who would [blank_start]prefer[blank_end] this after an acute episode 2. to avoid [blank_start]non-adherence[blank_end] (either intentional or unintentional) 3. if an antipsychotic medication is a clinical [blank_start]priority[blank_end] within the treatment plan (forensic/[blank_start]compulsory treated[blank_end] patients) Switching from oral to LAIS: • For patients who’ve never taken injectable antipsychotics recommend that [blank_start]efficacy AND tolerability[blank_end] is first established with [blank_start]oral[blank_end] doses • Previous oral antipsychotics gradually discontinued from time of treatment initiation – [blank_start]cross titration[blank_end]

Some LAIs: 1. Aripiprazole Maintena Duration of action and time to steady state = [blank_start]6-8[blank_end] weeks. Tmax = [blank_start]7-24 days or 5-7 days[blank_end] with continuous therapy. Half-life = [blank_start]30[blank_end] days (300mg) or [blank_start]47[blank_end] days (400 mg). 2. Olanzapine palmoate Given every [blank_start]4 weeks[blank_end]. Suspension in solution injected into [blank_start]gluteal[blank_end] muscle. Duration of action = [blank_start]6[blank_end] weeks. Tmax = [blank_start]2-4 days[blank_end]. T ½ = [blank_start]30 days[blank_end]. Steady state = 12 weeks. 3. Paliperidone palmitate Major active metabolite of [blank_start]risperidone[blank_end], acts at D2 and 5-HT2A receptors. Duration of action ~[blank_start]4[blank_end] weeks. Tmax median [blank_start]13 days[blank_end]. Cmax is 28% higher with [blank_start]deltoid[blank_end] versus gluteal injection. [blank_start]Monthly[blank_end] dosing. Formulations mean no [blank_start]oral[blank_end] test needed first, but first dose is followed by the 2nd at day 8.

Select the appropriate reason for antipsychotic combinations:

Combo examples: Clozapine plus amisulpride Clozapine + [blank_start]aripiprazole[blank_end] – minimises cardiac and metabolic risks Clozapine + [blank_start]mirtazapine[blank_end] – improved negative symptoms in small RCT Clozapine + [blank_start]minocycline[blank_end] – significant effects on working memory, avolition and anxiety/depression