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

❌

Antidepressants:
• Sudden stop not recommended due to increased risk of ❌
• Slow tapering doesn’t always ❌ incidence/severity of discontinuation ❌
• Some may prefer abrupt stop and ❌
• All have the potential to cause withdrawal phenomena if taken ❌ weeks
• Cross ❌ preferred but low need if transferring between drugs of the same ❌ (ie can go from one SSRI to another abruptly)
• Co-administration of some antidepressants, even when cross-tapering, is absolutely contraindicated for example ❌.

Follow the Maudsley's guidelines and consider half lives.

Antipsychotics
TDM -
• Plasma concentration don’t necessarily ❌ brain concentration which can be up to 20 times ❌
• TDM ❌ 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 ❌.

• After 1-2 years of taking an antipsychotic following a first episode and remaining well, the risk of relapse remains high - up to ❌% risk per month
• If withdrawing an antipsychotic after 1 year, the risk of relapse is ~ ❌% and after 2 years ❌%
• All psychotics cause discontinuation after some time.
• ❌ is better for managing long-term CV risk and mortality
• Maudsley states ‘if a patient has alreadytried ❌ the benefits of switching rather than staying could be marginal’
• Clozapine, olanzapine worst for ❌
• Chlorpromazine, haloperidol worst for ❌

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

• Offer a LAIs (Long-acting injections or depots) to those;
1. who would ❌ this after an acute episode
2. to avoid ❌ (either intentional or unintentional)
3. if an antipsychotic medication is a clinical ❌ within the treatment plan (forensic/❌ patients)

Switching from oral to LAIS:
• For patients who’ve never taken injectable antipsychotics recommend that ❌ is first established with ❌ doses
• Previous oral antipsychotics gradually discontinued from time of treatment initiation – ❌

Some LAIs:

1. Aripiprazole Maintena
Duration of action and time to steady state = ❌ weeks. Tmax = ❌ with continuous therapy. Half-life = ❌ days (300mg) or ❌ days (400 mg).

2. Olanzapine palmoate
Given every ❌. Suspension in solution injected into ❌ muscle. Duration of action = ❌ weeks. Tmax = ❌. T ½ = ❌. Steady state = 12 weeks.

3. Paliperidone palmitate
Major active metabolite of ❌, acts at D2 and 5-HT2A receptors. Duration of action ~❌ weeks. Tmax median ❌. Cmax is 28% higher with ❌ versus gluteal injection. ❌ dosing. Formulations mean no ❌ test needed first, but first dose is followed by the 2nd at day 8.

Combo examples:
Clozapine plus amisulpride
Clozapine + ❌ – minimises cardiac and metabolic risks
Clozapine + ❌ – improved negative symptoms in small RCT
Clozapine + ❌ – significant effects on working memory, avolition and anxiety/depression