Four Pathways, Four Consequences — and the Movement Clock

Block a pathway

Agents, and what each one makes you watch for

Agent	Class note	Watch especially for
Haloperidol, fluphenazine	First generation, high potency	Acute dystonia, akathisia, pseudoparkinsonism, tardive dyskinesia, raised prolactin; QT with intravenous use
Chlorpromazine	First generation, low potency	Sedation, orthostatic hypotension, anticholinergic load, photosensitivity
Risperidone, paliperidone	Second generation	Highest prolactin elevation of the second generation; dose-dependent movement effects
Olanzapine	Second generation	Greatest weight gain and metabolic burden; sedation
Quetiapine	Second generation	Sedation, orthostasis, weight gain; low movement risk
Ziprasidone	Second generation	QT prolongation; take with a meal of about 500 calories or it is not absorbed
Lurasidone	Second generation	Akathisia; take with at least 350 calories of food
Aripiprazole, brexpiprazole, cariprazine	D2 partial agonists	Akathisia, activation, insomnia; least metabolic burden of the group
Clozapine	Reserved for treatment resistance	Agranulocytosis, myocarditis, seizures, severe constipation and ileus, sialorrhea, metabolic effects, orthostasis

Long-acting injectables are not punishment. Depot haloperidol, fluphenazine, risperidone, paliperidone and aripiprazole reduce relapse and rehospitalisation and are especially useful after a first episode. Frame them as a way to stop thinking about pills every day — never as a consequence of missed doses. The framing predicts whether the person accepts it.

The movement clock

Rigidity with fever: which emergency is this?

	Neuroleptic malignant syndrome	Serotonin syndrome
Trigger	Antipsychotic started, increased, switched or given intramuscularly	A serotonergic agent started, raised or combined
Onset	Days, usually within the first two weeks	Hours
Muscle tone	Generalised lead-pipe rigidity	Rigidity that is lower-limb predominant
Reflexes	Normal or reduced	Hyperreflexia and clonus, often ocular or lower-limb
Also	Markedly raised creatine kinase, raised white count, myoglobinuria	Myoclonus, tremor, mydriasis, diarrhoea, active bowel sounds
Skin	Diaphoretic	Diaphoretic

Nursing sequence in neuroleptic malignant syndrome. Hold every antipsychotic dose — that is a nursing action you take before the order arrives. Call rapid response and the prescriber. Full vital signs including a core temperature. Begin cooling. Secure intravenous access for aggressive fluids. Monitor urine output for myoglobinuria. Anticipate creatine kinase, CBC and CMP, dantrolene or bromocriptine, and transfer to intensive care. A temperature above 38 degrees Celsius on two occasions is enough to raise the alarm.

Anticholinergic toxicity is the third thing in the room and it is separated by the skin and the bowel: dry skin and absent bowel sounds. Both syndromes above give you sweating, and serotonin syndrome gives you active bowels. And remember malignant catatonia, which is clinically indistinguishable from neuroleptic malignant syndrome — another reason a person who stops moving, speaking and eating gets a medical response, not a behavioural one.

Clozapine, and the monitoring nobody applauds

Monitoring	Baseline	Then
Weight, BMI, waist	Yes	Every visit for six months, then quarterly
Blood pressure, fasting glucose or A1c	Yes	At twelve weeks, then annually
Fasting lipid panel	Yes	At twelve weeks, then annually
AIMS	Yes	Every six months on first-generation agents, every twelve on second-generation
Absolute neutrophil count	Yes	Weekly for six months, every two weeks for six months, then monthly under REMS — no current count, no dispensed dose
ECG	If cardiac risk, or on ziprasidone, intravenous haloperidol or clozapine	With dose changes and any added QT-prolonging drug
Prolactin	If symptomatic	With galactorrhea, amenorrhea or sexual dysfunction

Fever or sore throat on clozapine is a neutrophil count today, not a symptomatic treatment for a cold. Myocarditis arrives mostly in the first two months — new chest pain, breathlessness, tachycardia out of proportion, fever, fatigue — and needs troponin, C-reactive protein and echocardiography. Severe constipation progressing to ileus is a genuine cause of death, so a bowel regimen starts prophylactically and bowel movements are documented.

The trap that catches whole teams. Smoking induces CYP1A2. When a person stops smoking — on admission to a smoke-free unit, for instance — clozapine and olanzapine levels rise, and toxicity can follow within days. Flag every new admission who has just stopped smoking.

And say the timing out loud to the person. Days for agitation and sleep. One to two weeks before positive symptoms begin to shift. Four to six weeks or more for a full response. Negative and cognitive symptoms respond least and slowest. Someone who expects relief in two days and gets akathisia instead will stop the drug within a week — and will be charted as declining treatment rather than as under-informed.