Antipsychotics, clozapine and long-acting injectables

1. Introduction

Version followed: US Clozaril prescribing information (revised June 2025) and FDA Drug Safety Communication of 27 August 2025 (clozapine REMS removed, effective 13 June 2025); UK clozapine SmPC (Clozapine Viatris orodispersible, revised February 2026); NICE CG178 Psychosis and schizophrenia in adults (2014, minor updates to December 2021) with NICE QS80; APA Practice Guideline for the Treatment of Patients With Schizophrenia, 3rd edition (2020). Regulatory status checked as of October 2026 against these sources.

Antipsychotics, including clozapine and long-acting injectable (depot) formulations, are prescriber-delivered medicines. This guide is written for the psychotherapist working alongside the prescriber and the mental health team, not for prescribing. It contains no doses, titration, schedules, switching, stopping or combination guidance; every decision about starting, continuing, changing or stopping a medicine belongs to the client and the prescriber. [source: NICE CG178 1.3.5.1; APA 2020]

• What it is. Antipsychotic medication is recommended by the APA (statement 4, rated 1A) and NICE as a core treatment for schizophrenia, within a person-centred plan that also includes psychosocial treatment. Clozapine is the medicine guidelines reserve for treatment-resistant schizophrenia. In the US it is also labelled for reducing recurrent suicidal behaviour in schizophrenia or schizoaffective disorder. Long-acting injectables (LAIs) are the same or related medicines given as an injection at intervals by a clinician, usually a nurse in a clinic, instead of daily tablets. [source: APA 2020 statements 4, 7, 8, 10; Clozaril USPI 2025; Krishna et al. 2024]
• How change happens, as the sources frame it. The medicine reduces psychotic symptoms and the risk of relapse. Clozapine is described by NICE as the only drug with established benefit for treatment-resistant illness. Guidelines expect medication to work alongside CBT for psychosis (CBTp), family intervention and other psychosocial care. A collaborative relationship, careful monitoring and the client's informed choice support continued, safe treatment. [source: NICE QS80 statement 4; NICE CG178 1.3.4.1; APA 2020]
• Who delivers it and regulatory status.
  • Prescribing: psychiatrists or other prescribers in secondary care, with physical-health monitoring shared with primary care. NICE keeps monitoring in secondary care for at least 12 months or until the person is stable, whichever is longer. [source: NICE CG178 1.3.6.5, 1.5.3.2]
  • United States: clozapine carries a boxed warning (see 4.A2). The clozapine REMS was removed effective 13 June 2025. Prescribers, pharmacies and patients no longer enrol in a REMS, and ANC results are no longer reported to one. ANC monitoring is still recommended according to the prescribing information. [source: FDA DSC 27 Aug 2025]
  • United Kingdom: the SmPC restricts clozapine to patients registered with the brand's patient monitoring service, prescribed under an appropriate specialist and dispensed by registered pharmacies. Each patient should be on one brand and registered only with that brand's service. [source: Clozapine SmPC UK 2026]
  • Other jurisdictions (EU/EMA, Australia, Canada): not checked for this guide [uncertain]; ask the treating team which local rules apply.
  • Injectables: given by clinicians in clinics or at home. One olanzapine LAI has its own US REMS with mandatory post-injection observation at certified facilities (see 4.A3). [source: FDA DSC 2015 PDSS]
• Scope note. Psychedelic-assisted and ketamine-assisted psychotherapies are not covered here; they are in Domain VII.

2. Framework

The medical treatment has no psychotherapy "phases". The stages below are a framework for the therapist's parallel work, built around the prescriber's process as the guidelines describe it. [synthesis, structured on NICE CG178 1.3.5–1.3.6, 1.5.5–1.5.7 and the clozapine labelling]

Psychotherapy dose and format (per NICE CG178): CBTp one-to-one, following a manual, at least 16 planned sessions, offered starting in the acute phase or later (including inpatients). Family intervention for families in close contact: 3 months to 1 year, at least 10 planned sessions, including the client where practical. Consider arts therapies, especially for negative symptoms, preferably in groups. NICE does not routinely recommend counselling, supportive psychotherapy, adherence therapy or social skills training as specific interventions (APA 2020 instead suggests supportive psychotherapy and social skills training, rated 2C). Where versions differ, this guide follows NICE for session structure. [source: NICE CG178 1.3.7.1–1.3.7.2, 1.4.4.1–1.4.4.8; APA 2020 statements 16–24]

If the client wants psychological treatment without medication: NICE says to tell them psychological interventions work better alongside antipsychotics. If they still choose this, NICE says to offer family intervention and CBT, agree a team review of the options (including medication) within a month or less, and monitor symptoms, distress and functioning regularly. The therapist arranges for that review to happen with the team and does not judge the medication question themselves. [source: NICE CG178 1.3.4.2]

3. Guiding principles

• Stay in your lane on prescribing. Never tell a client, or imply, that they should start, stop, reduce, increase, skip or switch a medicine; take every such question to the prescriber. Practical meaning: "That's an important question for Dr X. Let's work out how you'll put it to them." [synthesis]
• The choice is shared, and the client is the main voice. NICE says the client and prescriber choose the medicine together, with carers if the client agrees. Practical meaning: help the client know what they want and ask for it; don't advocate for a particular medicine or formulation. [source: NICE CG178 1.3.5.1]
• Work with a person-centred plan that combines both. The APA and NICE set medication inside a documented plan that includes psychosocial treatment. Practical meaning: position therapy as part of the plan, not as a rival to medication. [source: APA 2020 statement 3; NICE 1.3.4.1]
• Safety signals get passed on the same day. The labelling lists warning signs (infection or fever on clozapine, chest pain or palpitations, severe constipation, fainting, high fever) that need prompt medical assessment. Practical meaning: know the list, ask about it, and know who to call. [source: Clozaril USPI 2025; SmPC UK 2026]
• Respect ambivalence and treat it as information. Mixed feelings about medicines are common and often come from limited information or past coercion. Practical meaning: explore them openly and without judgement, and encourage the client to raise them with the prescriber. [source: Fiore et al. 2021] [synthesis]
• Be trauma-aware about coercion. Involuntary or crisis injections can be experienced as traumatic and can shape later refusal. Practical meaning: ask about the history of injections and restraint; validate it; involve the team in reducing coercive experiences. [source: Fiore et al. 2021]
• Give balanced, accurate information and correct myths. Clients often didn't know LAIs were an option or held myths about them. Practical meaning: share the official patient information and help the client prepare questions. [source: Fiore et al. 2021]
• Physical health is part of mental health care. NICE requires baseline and ongoing metabolic, cardiovascular and movement monitoring. Practical meaning: ask whether checks have happened and support attendance; no diet, weight or exercise targets from the therapist. [source: NICE CG178 1.3.6.1–1.3.6.4, 1.5.3.2–1.5.3.4]
• Information sharing needs consent and a plan. NICE expects care plans written with the service user and monitoring results shared between primary care and the psychiatrist. Practical meaning: agree in writing what you will pass on, to whom, and when you would act without delay (risk to life). [source: NICE 1.3.3.4, 1.5.3.2] [synthesis on consent mechanics]
• Keep psychotherapy going through medication changes. NICE offers CBTp and family intervention in the acute phase, recovery and remission alike. Practical meaning: don't pause therapy because medication is being reviewed. [source: NICE 1.4.4.1, 1.5.4.1]
• Labelling changes; check, don't rely on memory. For example, US clozapine REMS ended in 2025, but the boxed warning and ANC monitoring did not. Practical meaning: tell clients to read the current Medication Guide or leaflet and check with the pharmacist. [source: FDA DSC 27 Aug 2025; FDA DSC 2015 PDSS]

4. Intervention inventory

Part A describes how the treatment is delivered, as the labelling and guidelines publish it, so the therapist can understand and talk about it. It is not instructions. Part B covers the psychotherapist's own interventions.

A1. Antipsychotic treatment in general (prescriber-delivered)

• Purpose / when used: first-line and maintenance treatment of schizophrenia and other psychoses, within a person-centred plan. APA recommends continuing an antipsychotic when symptoms have improved (1A). [source: APA 2020 statements 4–6]
• How it is delivered (descriptive):
  • The prescriber and client choose the medicine together after discussing the benefits and the metabolic, extrapyramidal, cardiovascular, hormonal and other side effects. [NICE 1.3.5.1]
  • Before starting, NICE lists baseline checks: weight, waist, pulse, blood pressure, fasting glucose or HbA1c, lipids, prolactin, movement disorders, and nutrition, diet and activity. An ECG is offered when the product information specifies one, when there is cardiovascular risk or disease, or on inpatient admission. [NICE 1.3.6.1–1.3.6.2]
  • Each medicine is treated as an explicit individual trial with expected benefits and tolerable side effects recorded. Physical checks are repeated frequently in the first months and then at least yearly, alongside reviews of response, side effects, movement disorders and adherence. [NICE 1.3.6.3–1.3.6.4]
  • The APA guideline includes prescriber-managed options for acute dystonia, parkinsonism, akathisia and tardive dyskinesia. [APA 2020 statements 11–14]
• Class warnings to know (per the sources):
  • Increased mortality in elderly people with dementia-related psychosis: a boxed warning; antipsychotics are not approved for this use. [Clozaril USPI 2025; Krishna et al. 2024]
  • Neuroleptic malignant syndrome (NMS): a potentially fatal reaction requiring emergency care; the labelling says to consider it in anyone with high fever. NMS is commonly described as high fever with muscle rigidity, confusion or altered consciousness, and unstable pulse or blood pressure. [Clozaril USPI 2025; SmPC UK 2026; Krishna et al. 2024] [uncertain: the full feature list beyond high fever]
  • Tardive dyskinesia: involuntary movements; risk rises with longer treatment and greater cumulative exposure. [Clozaril USPI 2025]
  • Metabolic changes: hyperglycaemia and diabetes, dyslipidaemia and weight gain; glucose, lipids and weight are monitored. [Clozaril USPI 2025; NICE 1.3.6.4]
  • QT prolongation is noted for some agents (e.g., paliperidone, clozapine). [Krishna et al. 2024; Clozaril USPI 2025]
• Watch for (therapist): new restlessness, stiffness, tremor, abnormal mouth or face movements, sedation, weight or appetite change, sexual or menstrual changes, and dizziness on standing. Pass these on to the prescriber rather than interpreting them. [synthesis from the side-effect categories in NICE 1.3.5.1]

A2. Clozapine (prescriber-delivered; specialist supervision)

• Purpose / when used:
  • US label: severely ill patients with treatment-resistant schizophrenia; reducing the risk of recurrent suicidal behaviour in schizophrenia or schizoaffective disorder. It is reserved for these uses because of the neutropenia and seizure risks. [Clozaril USPI 2025]
  • UK SmPC: treatment-resistant schizophrenia (including people with severe neurological reactions to other antipsychotics) and psychosis in Parkinson's disease where standard treatment has failed. [SmPC UK 2026]
  • Guidelines: NICE offers it after at least two adequate antipsychotic trials, one a non-clozapine second-generation drug. NICE quality standard QS80 makes offering it a measured quality statement. APA recommends it for treatment-resistant schizophrenia (1B) and for persisting substantial suicide risk (1B), and suggests it for persisting substantial risk of aggression (2C). [NICE 1.5.7.2; QS80; APA 2020 statements 7–9]
• US boxed warnings (headings): severe neutropenia; orthostatic hypotension, bradycardia and syncope; seizure; myocarditis, pericarditis and cardiomyopathy; increased mortality in elderly patients with dementia-related psychosis. [Clozaril USPI 2025]
• Blood (neutrophil) monitoring, as sources state it:
  • Baseline counts are required before starting, with regular monitoring throughout, most frequent at the start. Treatment may be interrupted or stopped, or a haematology opinion sought, depending on results. The risk of severe neutropenia is highest in the first months; the labelling cites the first 18 weeks. FDA says the risk "never goes away". [Clozaril USPI 2025; FDA DSC 27 Aug 2025]
  • US, since 13 June 2025: no REMS enrolment, no ANC reporting to a REMS, and pharmacists no longer verify ANC before dispensing. Prescribers should still follow the monitoring in the prescribing information, and a new Medication Guide was issued. [FDA DSC 27 Aug 2025]
  • UK: registration with the brand's monitoring service; counts checked frequently in the first 18 weeks and less often afterwards, but throughout treatment and for 4 weeks after stopping or until counts recover. People who stop for blood reasons must not be rechallenged. [SmPC UK 2026]
  • Benign ethnic neutropenia (Duffy-null associated neutrophil count): the US label says these patients have lower baseline counts but are not at higher risk of infection or of clozapine-induced neutropenia, and gives them separate baseline and monitoring tables. [Clozaril USPI 2025]
• Other warnings in the labelling:
  • Myocarditis and cardiomyopathy: myocarditis mostly appears in the first 2 months, cardiomyopathy usually later; some cases are fatal. Signs include chest pain, fast heartbeat or palpitations, shortness of breath, fever, flu-like symptoms, low blood pressure, swelling, or (UK) persistent resting tachycardia and unexplained fatigue. If myocarditis is suspected, clozapine is stopped and the person is referred urgently for cardiac assessment. [Clozaril USPI 2025; SmPC UK 2026]
  • Gastrointestinal hypomotility: constipation can progress to obstruction, ischaemia, perforation or death; it is to be recognised and treated promptly. [Clozaril USPI 2025; SmPC UK 2026]
  • Seizures: related to dose; avoid activities where sudden loss of consciousness is dangerous, such as driving. [Clozaril USPI 2025]
  • Other: orthostatic hypotension and falls; fever (usually benign, but evaluate for infection, neutropenia and NMS); eosinophilia; QT prolongation; anticholinergic toxicity; hypersalivation (very common); metabolic changes; DRESS (a severe skin reaction, UK); and psychosis recurrence or cholinergic rebound if stopped abruptly. [Clozaril USPI 2025; SmPC UK 2026]
  • Smoking and caffeine: tobacco smoke lowers clozapine levels. Stopping smoking, or switching to e-cigarettes (UK SmPC), can raise levels and side effects, so the prescriber needs to know about any change in smoking. Caffeine also interacts. [Clozaril USPI 2025; SmPC UK 2026]
  • Missed doses: the US Medication Guide tells patients who miss a day or more to contact the prescriber rather than restarting on their own. [Clozaril USPI 2025]
• What patients are told to report: fever or chills, flu-like feeling, extreme tiredness, mouth or skin sores, slow-healing wounds, urinary or vaginal symptoms, abdominal pain or bloating; dizziness, fainting, slow or irregular heartbeat; chest pain, palpitations, breathlessness, swelling; constipation, nausea, vomiting or abdominal swelling; excessive thirst, urination or hunger. [Clozaril USPI 2025 Medication Guide content; FDA DSC 27 Aug 2025]

A3. Long-acting injectable (depot) antipsychotics (prescriber-prescribed, clinician-administered)

• Purpose / when used: NICE: consider an LAI when the person prefers it after an acute episode, or when avoiding covert non-adherence is a clinical priority. Choose using the same criteria as for oral medicines and take into account the person's preferences about injections and how services are organised. APA suggests an LAI when the patient prefers it or has a history of poor or uncertain adherence (2B). [NICE 1.5.5.3, 1.5.6.1; APA 2020 statement 10]
• Formulations named in US sources: injectable forms of aripiprazole (including aripiprazole lauroxil), paliperidone, risperidone, haloperidol decanoate and fluphenazine decanoate, plus an olanzapine LAI. Some require an oral overlap at the start and some do not; that is the prescriber's decision. [Krishna et al. 2024] [uncertain: list current as of 2024; newer products not checked]
• How it is delivered (descriptive): given by a nurse or other clinician in a clinic or at home at set intervals. Clients describe the clinic as a predictable place, and the named nurse can be a source of continuity and support. [Phillips & McCann 2007; Fiore et al. 2021]
• Olanzapine LAI and post-injection delirium/sedation syndrome (PDSS): a boxed warning describes sedation (possibly progressing to coma) and/or delirium after injection. The US REMS requires a certified facility with emergency access, observation for at least 3 hours after each injection, and an escort to the next destination. Signs include unusual sleepiness, dizziness, confusion, trouble speaking or walking, weakness, anxiety, raised blood pressure, seizures and loss of consciousness. [FDA DSC 23 Mar 2015] [uncertain: current REMS status after 2015 not verified; check the current label]
• Benefits and drawbacks reported by clients: clients value not having to remember daily tablets (a daily reminder of illness), a sense of safety and fewer relapses. Concerns include coercion (especially first injections given during involuntary admission), needle fear and injection pain, stigma ("for severe illness"), lack of information, short consultations, and time off work for appointments. [Fiore et al. 2021]
• Class warnings: as A1, including the boxed warning on mortality in elderly people with dementia-related psychosis. [Krishna et al. 2024]

B1. Recognising when to suggest a medical or psychiatric review

• Purpose / when to use: whenever a client describes possible warning signs, new or returning psychotic symptoms, or questions about their medicine. [synthesis; warning signs per sources cited]
• Steps:
  1. Keep a one-page list of the labelled warning signs (A1–A3) and team contact numbers in the client's file.
  2. Sort what you hear into three groups [synthesis]:
     • Emergency now (urge same-day emergency care and inform the team): high fever, especially with stiffness or confusion; chest pain, breathlessness or fainting; severe abdominal pain, swelling or vomiting with constipation on clozapine; seizure; heavy sedation or confusion after an olanzapine LAI injection.
     • Same-day contact with prescriber or clozapine clinic: fever, sore throat, mouth sores or flu-like illness on clozapine; palpitations; constipation lasting days on clozapine; missed clozapine doses; stopping or starting smoking on clozapine.
     • Raise at the next review (or sooner if the client wishes): weight gain, restlessness, abnormal movements, sexual side effects, sedation, persistent symptoms.
  3. Tell the client which group it falls into and why, citing the leaflet rather than your opinion.
  4. Agree who calls: the client, you with the client present, or you with consent. Document it.
  5. Follow up at the next contact.
• Example language (illustrative): "Fever on clozapine is one of the things the leaflet says to report straight away. Shall we ring the clinic together now?"
• Watch for: your own reluctance to "medicalise". With these drugs, false alarms are cheap and missed infection or myocarditis is not.

B2. Referral and collaborative care

• Purpose / when to use: at intake for anyone with psychosis not linked to a team; whenever treatment resistance, safety concerns or significant side effects arise. [source: APA 2020 statements 1–3, 15; NICE 1.4.1.1–1.4.1.3]
• Steps:
  1. For first-episode psychosis, refer to coordinated specialty care / early intervention services. APA recommends this (1B). [APA 2020 statement 15]
  2. Get written consent specifying what you share (side effects observed, risk changes, therapy goals), with whom (prescriber, care coordinator, GP) and how often.
  3. Send a brief, factual, observation-based note: what the client reported, in their words, and what you advised ("to contact you"). Avoid medication recommendations. [synthesis]
  4. Ask to be included in care-plan reviews and the crisis section of the care plan; NICE expects care plans to be written with the service user. [NICE 1.3.3.4, 1.5.3.6]
  5. Where non-response is being considered, make sure the team knows what psychological treatment has been delivered. NICE asks for this review before clozapine. [NICE 1.5.7.1]
• Example language (illustrative): "I'd like to let your psychiatrist know about the dizziness you've mentioned. What would you be comfortable with me saying?"
• Watch for: the client feeling talked about. Share copies of letters with them where possible. [synthesis]

B3. Psychoeducation about the medicine and its monitoring

• Purpose / when to use: when a medicine is offered or started, after changes, and when the client is confused or frightened. APA recommends psychoeducation (1B). [APA 2020 statement 17]
• Steps:
  1. Ask what the client already knows, believes and has heard (including online myths, e.g., that injections are for "dangerous" people or link to addiction). [Fiore et al. 2021]
  2. Use the official Medication Guide or patient leaflet, which the client should reread because it changes (FDA asks patients to read it before each olanzapine LAI injection). Go through why monitoring happens (for clozapine, the blood test catches neutropenia early), what to report, and who to contact. [FDA DSC 2015, 2025]
  3. Explain plainly what changed in US clozapine rules in 2025: no REMS enrolment, but blood monitoring continues as the prescriber directs. [FDA DSC 27 Aug 2025]
  4. Note questions for the prescriber; do not answer questions about doses or changes.
  5. Teach-back: ask the client to explain in their own words when they would call the clinic.
• Example language (illustrative): "The leaflet says the blood tests are there to catch a drop in infection-fighting cells early. What do you make of that?"
• Watch for: information overload in acute states. Use short, repeated sessions and involve carers if the client agrees. [synthesis]

B4. Supporting informed consent and shared decision-making

• Purpose / when to use: before medication appointments in which a new medicine, clozapine or an LAI is discussed. NICE requires joint choice; clients report consultations as too short. [source: NICE 1.3.5.1; Fiore et al. 2021]
• Steps:
  1. Help the client clarify their values and priorities: which effects matter most (e.g., weight, sedation, sexual function, fewer hospital admissions, not taking pills daily, avoiding needles). Fiore et al. note sedation is a problem for some and a benefit for others.
  2. Build a written question list. Examples (illustrative): What benefits should I expect and when? Which side effects should I report? What monitoring is needed and how often? What are my other options, including tablets versus injections? What happens if I want to stop?
  3. Rehearse raising disagreement or preferences (role-play).
  4. Offer to attend or help the client bring a supporter, if the client wants and the service allows.
  5. Afterwards, debrief: what was decided, does the client feel heard, what remains unclear.
  6. Capacity and legal frameworks (e.g., involuntary treatment, community treatment orders) vary by jurisdiction and were not reviewed for this guide [uncertain]. Ask the team about the client's legal status and rights and refer to advocacy services. [synthesis]
• Example language (illustrative): "It's your decision with Dr X, not mine. What do you most want them to understand about what matters to you?"
• Watch for: the therapist's own views leaking in (praise for "good compliance", disappointment at hesitation). Neutrality supports genuine consent. [synthesis]

B5. Ambivalence and adherence conversations (never advising a change)

• Purpose / when to use: when a client hints at missing doses, wanting to stop, or feeling forced. Non-adherence is described as the greatest risk factor for psychotic relapse, and NICE does not routinely recommend a stand-alone adherence therapy. Here the goal is honest exploration and getting the conversation to the prescriber, not persuasion. [source: Krishna et al. 2024; NICE 1.4.4.6–1.4.4.8] [synthesis on method]
• Steps (MI-consistent, illustrative structure):
  1. Normalise mixed feelings and invite honesty without consequence in the room.
  2. Explore both sides: what the medicine gives and costs the client (identity, side effects, stigma, meaning of illness, past coercion).
  3. Reflect and summarise without steering towards a decision.
  4. Ask about actual current use. If the client has already stopped or reduced, do not advise either way; explain that the labelling and NICE flag risks around stopping (relapse; for clozapine, rebound effects, and the need to contact the prescriber before restarting) and that the prescriber should know. Help them make contact today. [Clozaril USPI 2025; NICE 1.4.6.3]
  5. Agree what the client will tell the prescriber, and plan relapse monitoring together (B9).
• Example language (illustrative): "Part of you wants a break from the tablets, and part of you remembers last winter. Both make sense. Who could you think this through with on the medical side, and when?"
• Watch for: a client concealing non-adherence from the team because of fear of coercion. Name the dilemma and help them find a safe way to disclose. [synthesis]

B6. Depot / LAI conversations, including coercion

• Purpose / when to use: when an LAI is offered, after involuntary injections, and in ongoing work with clients on depots. [source: Fiore et al. 2021; NICE 1.5.6.1]
• Steps:
  1. Ask about the history: first injection in what circumstances? Restraint, involuntary admission, family pressure? How was it for them? Fiore et al. found that early coercive injections could be traumatic and lead to later refusal.
  2. Validate and, where indicated, assess for trauma symptoms linked to treatment experiences. Offer trauma-focused work in the psychological plan where appropriate. [synthesis]
  3. Check for information gaps: did they know oral and injectable options both exist; do they know what their injection is and what to report?
  4. Address needle fear and pain. Explore coping strategies and help the client ask the nurse about adjustments that may help (the nurse decides on the clinical aspects). Graded exposure work for needle phobia can be offered as psychotherapy with consent, after checking for a fainting history. [synthesis]
  5. Address stigma and the meaning of an injection ("I must be really ill"; secrecy from others). [Fiore et al. 2021]
  6. Help the client turn preferences (e.g., setting, timing, a consistent named nurse) into requests to the team. NICE asks prescribers to weigh preferences about injections and service organisation. [NICE 1.5.6.1]
  7. Where treatment is legally mandated, help the client understand their rights and access advocacy and review processes. Local legal detail was not reviewed [uncertain].
• Example language (illustrative): "You've said the first injection happened while you were held down. That sounds frightening. How does it affect how you feel about the clinic now?"
• Watch for: the therapist becoming an enforcer of attendance. Keep the role of listener and supporter of choice, and say so to the team. [synthesis]

B7. Clozapine-specific support

• Purpose / when to use: from the first discussion of clozapine onwards, especially during the higher-risk early months. [source: Clozaril USPI 2025; SmPC UK 2026]
• Steps:
  1. Explore the meaning of being offered clozapine (hope, a "last resort", fear) and the burden of regular blood tests.
  2. Support blood-test attendance practically (planning, reminders the client chooses) and emotionally (needle anxiety, as B6 step 4). [synthesis]
  3. At each session in the early months, ask briefly about infection signs, chest symptoms and palpitations, dizziness and constipation. Pass on anything reported (B1).
  4. Ask about smoking changes (quitting, cutting down, starting to vape, or smoke-free hospital admission) and prompt the client to tell the prescriber. [SmPC UK 2026; Clozaril USPI 2025]
  5. Discuss driving and risky activities, with the advice to check with the prescriber (seizure risk). [Clozaril USPI 2025]
  6. Validate distressing common effects (hypersalivation, sedation, weight change) and support the client to report them; don't minimise. [SmPC UK 2026]
• Example language (illustrative): "Any fevers, sore throat, or bowel problems since last week? Those are on the leaflet's report-quickly list."
• Watch for: constipation being embarrassing to mention. Normalise asking about it directly. [synthesis]

B8. Monitoring and passing on side effects and warning signs

• Purpose / when to use: routinely throughout treatment. NICE lists side effects, movement disorders, adherence and physical health among the things to monitor. [source: NICE 1.3.6.4]
• Steps:
  1. Agree a brief check-in at the start of sessions covering sleep, sedation, restlessness, movements, appetite or weight concerns, sexual function, dizziness, mood and (for clozapine) infection, chest and bowel symptoms. [synthesis based on NICE side-effect domains]
  2. Record the client's own words and the onset date.
  3. Pass on according to the B1 urgency groups and your consent agreement.
  4. Ask whether the scheduled physical checks have happened (NICE baseline, 12-week and annual checks; primary-care checks at least annually) and support attendance. [NICE 1.3.6.4, 1.5.3.2]
  5. Address the psychological impact of side effects (body image with weight gain, shame about movements), without diet, weight or exercise targets. [synthesis]
• Example language (illustrative): "You mentioned your legs feel like they have to keep moving. That's worth telling the prescriber. Shall I add it to my note, or would you like to raise it yourself?"
• Watch for: misattributing side effects (e.g., akathisia mistaken for anxiety or agitation, sedation mistaken for low motivation or negative symptoms). Describe, don't diagnose; let the prescriber assess. [synthesis]

B9. Crisis, relapse-prevention and safety planning

• Purpose / when to use: early in therapy and updated after any crisis or medication change. [source: NICE 1.4.1.1–1.4.1.3, 1.5.3.6] [synthesis on plan content]
• Steps:
  1. Build a relapse signature with the client: their personal early signs, from past episodes (sleep change, suspiciousness, withdrawal, specific voices content) and as reported by carers if the client agrees.
  2. Agree an action plan for each level: self-care steps, who to tell, when to contact the prescriber or crisis team (NICE names crisis resolution and home treatment teams as first-line for acute crises).
  3. Include medication-related crisis steps as the leaflets state: e.g., contact the prescriber if doses are missed rather than restarting alone (clozapine); emergency care for the warning signs in B1. [Clozaril USPI 2025]
  4. Integrate suicide-risk assessment and safety planning to current standards; note that clozapine has a US indication for reducing recurrent suicidal behaviour, which is a prescriber matter. Lethal-means counselling covers safe storage of medicines with the team or carers, without method detail. [Clozaril USPI 2025; APA 2020 statement 8] [synthesis]
  5. Share the plan with the team (with consent) so it sits in the care plan's crisis section.
• Example language (illustrative): "Last time, the first sign was not sleeping and feeling that neighbours were watching. If that starts again, what would you want to happen, and who would you call?"
• Watch for: plans that exist only in the therapy file. The team and carers need a copy.

B10. Integrating psychotherapy for psychosis with medication

• Purpose / when to use: for all clients with psychosis or schizophrenia, from the acute phase onwards. [source: NICE 1.3.4.1, 1.4.4.1–1.4.4.3, 1.5.4.1–1.5.4.2; APA 2020 statements 16–24]
• Steps:
  1. Offer manualised CBTp (at least 16 sessions per NICE) and family intervention where the family is in close contact (3 months to 1 year, at least 10 sessions per NICE). Consider arts therapies, especially for negative symptoms. The procedures for these therapies are covered in their own guides [synthesis].
  2. Build medication experiences into the formulation: beliefs about illness and medicine, side effects as stressors, and the meaning of injections or clozapine.
  3. Use CBTp goals that matter whatever the medication (distress from voices, paranoia, functioning, recovery).
  4. Also consider supported employment (APA 1B), self-management programmes and peer support (NICE). [APA 2020 statement 18; NICE 1.1.6.1–1.1.6.2]
  5. If the client wants psychological treatment alone, follow NICE 1.3.4.2: explain the guideline's view and ensure the team arranges a review within a month or less. Do not make the medication judgement yourself.
• Example language (illustrative): "The medicine is your psychiatrist's area. Our work is about how the voices affect you and what you want your life to look like. The two can go side by side."
• Watch for: splitting ("therapy is good, meds are bad", or the reverse). Model a joined-up plan. [synthesis]

B11. Supporting physical health

• Purpose / when to use: throughout. NICE expects primary care and secondary care to identify and treat raised blood pressure, abnormal lipids, obesity, diabetes risk and inactivity. [source: NICE 1.5.3.2–1.5.3.4]
• Steps: ask whether checks happened, help the client book and attend, explore barriers (paranoia in waiting rooms, motivation), support behaviour change the medical team has proposed, and set no diet, weight or exercise targets yourself. [synthesis]
• Example language (illustrative): "Has the GP done your yearly blood tests and blood pressure? What would make that appointment easier?"
• Watch for: eating-disorder history or distress about weight. Flag it to the team. [synthesis]

B12. Support during prescriber-led changes and after treatment ends

• Purpose / when to use: when the prescriber and client decide to change or stop a medicine, or the client is discharged from the clozapine clinic or depot clinic. [source: NICE 1.4.6.3–1.4.6.5; SmPC UK 2026] [synthesis]
• Steps:
  1. Confirm the plan is the prescriber's and understood by the client; you do not give or reinterpret instructions.
  2. Increase the frequency of relapse-signature check-ins. NICE asks prescribers to monitor for relapse for at least 2 years after withdrawal; offer to share observations.
  3. For clozapine, remind the client that blood monitoring continues for a period after stopping, as the SmPC states, and support attendance.
  4. Process the change emotionally: relief, fear, identity ("am I still ill?").
  5. Keep or reinstate psychological work during the transition.
• Example language (illustrative): "You and Dr X have agreed a plan. Let's keep an eye on your early warning signs together as it goes along."
• Watch for: early relapse signs. Act on the crisis plan (B9) and contact the team.

B13. Working with carers and family around medication

• Purpose / when to use: where family is involved and the client consents. NICE considers carers' views in medication choice (with the client's agreement) and offers family intervention. Fiore et al. describe indirect family pressure around LAIs. [source: NICE 1.3.5.1, 1.3.7.2; Fiore et al. 2021]
• Steps: clarify the client's consent and boundaries for what is shared; give carers the official leaflet's warning-sign list and the crisis plan; explore family conflict about medication in family sessions without taking sides; encourage carers to raise concerns with the team, not to pressure the client. [synthesis]
• Example language (illustrative): "You both want things to go well. Can we look at how to talk about the injections without it becoming a fight?"
• Watch for: family pressure being experienced as coercion, or carers asked to supervise medication without the client's agreement. [synthesis]

5. Handling problems

The labelling and guidelines say little about psychotherapy process problems; most guidance below is [synthesis] grounded in the sources cited.

• Client asks you whether to stop, cut down or switch. Don't answer the medical question. Explore what's behind it, provide the leaflet information on risks of stopping, and help them contact the prescriber, ideally before acting. Document the conversation. [synthesis; NICE 1.4.6.3; Clozaril USPI 2025]
• Client has already stopped. Stay non-judgemental. Assess risk and early relapse signs, give the labelled reason to contact the prescriber promptly (for clozapine: not restarting on their own after missed doses), and activate the crisis plan if needed. [Clozaril USPI 2025] [synthesis]
• Stuck: persisting symptoms despite medication. Check that CBTp and family intervention have actually been offered and delivered. NICE asks for psychological treatment, adherence and other causes to be reviewed before clozapine, so share your information with the team. Keep therapy goals focused on distress and functioning. [NICE 1.5.7.1, 1.5.4.1] [synthesis]
• Resistance rooted in past coercion (forced injections, detention). Slow down; treat it as a possible trauma memory; validate; separate your role from enforcement; help the client bring requests for less coercive arrangements to the team; consider trauma-focused work. [Fiore et al. 2021] [synthesis]
• Rupture: client thinks you are "on the psychiatrist's side" (or the reverse). Name your role transparently (you do not prescribe, you pass on concerns with consent, you support their choice) and repair openly. [synthesis]
• Rupture with the team caused by information sharing. Revisit the consent agreement, show the client what was said, and agree how to handle future reports. Duty-to-protect and emergency exceptions to confidentiality follow your professional code and local law [uncertain: jurisdiction-specific].
• Overwhelm about clozapine monitoring or the warning-sign list. Prioritise the few report-now signs, use a card or phone note, link to the clinic nurse, and pace the information. [synthesis; warning signs per Clozaril USPI 2025]
• Needle phobia and blood-test or injection avoidance. Assess the fainting (vasovagal) history; offer graded exposure with consent and with medical staff aware; never pressure the client to attend. [synthesis]
• Non-attendance at depot clinic or blood tests. Explore barriers (work hours, travel, stigma, fear) without judgement; help the client request practical changes; inform the team only per the consent agreement or if there is a safety concern. In the UK, the SmPC links continued clozapine supply to registration and blood monitoring, so missed bloods can interrupt treatment; the client should speak to the clinic. [SmPC UK 2026] [synthesis]
• Side effects mistaken for psychological symptoms. Restlessness (possible akathisia), sedation, flattened affect or new movements: describe and pass on rather than formulate them as anxiety, avoidance or negative symptoms. [APA 2020 statements 11–14] [synthesis]
• Weight gain and body-image distress. Validate; ensure metabolic monitoring is happening; support medically proposed lifestyle changes without targets; screen for disordered eating and inform the team. [NICE 1.3.6.4, 1.5.3.3] [synthesis]
• Client starts or stops smoking, or enters a smoke-free hospital while on clozapine. Prompt the client or team to inform the prescriber; levels can change. [SmPC UK 2026; Clozaril USPI 2025]
• Client wants therapy instead of medication. Follow NICE 1.3.4.2: explain the guideline's view neutrally, provide CBTp and family intervention, and make sure the team arranges an early review. [NICE 1.3.4.2]
• Client relies on online or AI information about medication. Look at the material together, compare it with the official leaflet, and take open questions to the prescriber or pharmacist. [synthesis]
• Outdated information about rules (e.g., "I need to be enrolled in the REMS"). Explain the 2025 US change neutrally and check with the pharmacist; the boxed warning and monitoring still apply. [FDA DSC 27 Aug 2025]
• Therapist's own anxiety or strong views about psychiatric medicine. Use supervision; stay with the client's choice and the shared plan. [synthesis]

Sources

• FDA removes Risk Evaluation and Mitigation Strategy (REMS) program for the antipsychotic drug clozapine (Drug Safety Communication, 27 Aug 2025)
• Clozaril (clozapine) US Prescribing Information, revised June 2025 (FDA label, ref. 5608164)
• Clozapine Viatris orodispersible tablets: Summary of Product Characteristics, revised February 2026 (emc)
• NICE CG178 Psychosis and schizophrenia in adults: prevention and management (2014; copy hosted by NHS Scotland Right Decisions)
• NICE QS80 Quality statement 4: Treatment with clozapine
• American Psychiatric Association. The APA Practice Guideline for the Treatment of Patients With Schizophrenia (Focus, 2020)
• APA releases new practice guideline on treatment of patients with schizophrenia (APA news release, Sept 2020)
• FDA Drug Safety Communication: FDA review of study sheds light on two deaths associated with the injectable schizophrenia drug Zyprexa Relprevv (23 Mar 2015)
• Krishna A, et al. (2024). A comprehensive guide to long-acting injectable antipsychotics for primary care clinicians. J Am Board Fam Med 37(4):773 [uncertain: full author list]
• Fiore G, Bertani DE, Marchi M, Cardoso G, Galeazzi GM (2021). Patient subjective experience of treatment with long-acting injectable antipsychotics: a systematic review of qualitative studies. J Bras Psiquiatr 70(1):68–77
• Phillips L, McCann E (2007). The subjective experiences of people who regularly receive depot neuroleptic medication in the community. J Psychiatr Ment Health Nurs 14(6):578–586 (City Research Online record; abstract only)
• Not reviewed: the EMA, Australian (TGA) and Canadian clozapine requirements; current Zyprexa Relprevv REMS documents; mental health legislation on involuntary treatment and community treatment orders [uncertain].