const pptxgen = require("pptxgenjs");
const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Schizophrenia: Comprehensive Overview & Recent Guidelines";
pres.author = "Healthcare Education";

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  red:     "C0392B",   // warning/danger
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// ─── HELPER: add a styled section heading line ──────────────
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// ══════════════════════════════════════════════════════════════
// SLIDE 1 — TITLE SLIDE
// ══════════════════════════════════════════════════════════════
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s.addText("SCHIZOPHRENIA", {
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s.addText("A Comprehensive Clinical Overview", {
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s.addText("Diagnosis · Pathophysiology · Treatment · Recent 2024–2026 Guidelines", {
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s.addText("For General Healthcare Professionals", {
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s.addText("Sources: Harrison's 22E · Goodman & Gilman · Adams & Victor's · NICE 2025 · APA Guidelines 2020 · PubMed 2025", {
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s.addText("June 2025", {
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// ══════════════════════════════════════════════════════════════
// SLIDE 2 — OUTLINE
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Presentation Outline", "What we will cover today");
const topics = [
  "1.  Overview & Historical Background",
  "2.  Epidemiology & Global Burden",
  "3.  Etiology & Risk Factors",
  "4.  Neurobiology & Pathophysiology",
  "5.  Clinical Features: Positive, Negative & Cognitive Symptoms",
  "6.  DSM-5-TR Diagnostic Criteria",
  "7.  Differential Diagnosis",
  "8.  Subtypes & Related Disorders",
  "9.  Course & Prognosis",
  "10. Pharmacological Treatment — 1st & 2nd Generation Antipsychotics",
  "11. Treatment-Resistant Schizophrenia & Clozapine",
  "12. Side Effect Management",
  "13. Psychosocial & Non-Pharmacological Interventions",
  "14. Recent Guidelines: NICE 2025, APA, VA/DoD 2023",
  "15. Special Populations & Comorbidities",
  "16. Monitoring & Follow-Up",
  "17. Summary & Key Takeaways",
];
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 3 — OVERVIEW
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Overview & Historical Background", "From Dementia Praecox to Modern Understanding");
s.addText([
  bullet("Term 'dementia praecox' introduced by Emil Kraepelin (1896):", 0, true),
  subbullet("Described early-onset mental deterioration with chronic progressive course"),
  bullet("Eugen Bleuler (1911) coined 'Schizophrenia' (Greek: split mind):", 0, true),
  subbullet("Emphasized the 4 A's: Affect (flat), Associations (loose), Autism, Ambivalence"),
  bullet("Schizophrenia is a heterogeneous syndrome characterized by perturbations of:", 0, true),
  subbullet("Language, Perception, Thinking, Social activity, Affect, and Volition"),
  bullet("No pathognomonic features — diagnosis is based on clinical criteria", 0, false),
  bullet("DSM-5-TR (2022) & ICD-11 provide current diagnostic frameworks", 0, false),
  bullet("Accounts for the majority of psychiatric hospital beds globally", 0, false),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 4 — EPIDEMIOLOGY
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Epidemiology & Global Burden", "A worldwide health challenge");

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statBox(s, 4.9, 1.3, 2.1, 1.2, "$155.7B", "Annual Costs\n(Direct + Indirect, USA)", C.accent);
statBox(s, 7.2, 1.3, 2.1, 1.2, "50%", "Monozygotic Twin\nConcordance Rate", C.subText);

s.addText([
  bullet("Peak onset: Males 18–25 yrs; Females 25–35 yrs (second peak post-menopause)", 0, true),
  subbullet("Males tend to have earlier onset and more severe course"),
  bullet("Equal prevalence across sexes; found in every ethnic and social group", 0, false),
  bullet("35 new cases per 100,000 population annually worldwide", 0, false),
  bullet("Schizophrenic patients occupy ~50% of psychiatric hospital beds (Adams & Victor)", 0, false),
  bullet("6.6% risk in first-degree relatives; 40% if both parents affected", 0, false),
  bullet("Dizygotic twin concordance ~10%; genetic heritability estimated at 80%", 0, false),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 5 — ETIOLOGY & RISK FACTORS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Etiology & Risk Factors", "Multifactorial — genetic, developmental, environmental");
s.addText([
  bullet("GENETIC FACTORS", 0, true),
  subbullet("GWASs: several hundred small-effect risk loci; major CNVs (22q11.2 deletion)"),
  subbullet("Pathways: immunity, inflammation, synaptic signaling, cell signaling"),
  subbullet("Polygenic risk scores under investigation for clinical use"),
  bullet("NEURODEVELOPMENTAL FACTORS", 0, true),
  subbullet("Prenatal infection, obstetric complications, maternal malnutrition"),
  subbullet("Early developmental insults disrupt normal neural circuit formation"),
  subbullet("Winter/spring birth (slight increased risk): possibly viral exposure in utero"),
  bullet("ENVIRONMENTAL & SOCIAL FACTORS", 0, true),
  subbullet("Urbanicity: 2x risk in urban vs. rural environments"),
  subbullet("Cannabis use: dose-dependent risk, especially with high-THC products in adolescence"),
  subbullet("Childhood trauma, social adversity, migration/minority status"),
  subbullet("Increasing paternal age is an independent risk factor"),
  bullet("Epigenetic modifications also implicated in disease expression", 0, false),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 6 — NEUROBIOLOGY / PATHOPHYSIOLOGY
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Neurobiology & Pathophysiology", "Dopamine, Glutamate, Serotonin and beyond");

// two column layout
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s.addText("Other Neurotransmitter Systems", { x: 5.1, y: 1.3, w: 4.5, h: 0.45, fontSize: 15, bold: true, color: C.white, align: "center", fill: { color: C.accent }, fontFace: "Calibri" });
s.addText([
  bullet("Mesolimbic DA hyperactivity → Positive symptoms (hallucinations, delusions)", 0, false),
  subbullet("DA hyperfunction in striatum/nucleus accumbens"),
  bullet("Mesocortical DA hypofunction → Negative/cognitive symptoms", 0, false),
  subbullet("Reduced DA in prefrontal cortex"),
  bullet("All antipsychotics block D2 receptors in ventral striatum", 0, false),
  bullet("Psychostimulants (↑DA) worsen psychotic symptoms — supports hypothesis", 0, false),
  bullet("Brain gene expression in schizophrenia resembles aging — possible parallel mechanisms", 0, false),
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s.addText([
  bullet("GLUTAMATE (NMDA hypothesis)", 0, true),
  subbullet("NMDA receptor hypofunction → mimics schizophrenia (PCP, ketamine)"),
  subbullet("Explains negative + cognitive symptoms"),
  bullet("SEROTONIN (5-HT2A)", 0, true),
  subbullet("5-HT2A antagonism by SGAs reduces EPS & may improve negative symptoms"),
  bullet("GABA: reduced inhibitory interneurons in PFC", 0, true),
  bullet("Structural: enlarged lateral ventricles, reduced hippocampal & PFC volume", 0, true),
  bullet("Emerging: mGlu2/3, muscarinic M1/M4, α1/α2 noradrenergic targets", 0, false),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 7 — CLINICAL FEATURES: POSITIVE SYMPTOMS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Clinical Features: Positive Symptoms", "Productive symptoms — excess or distortion of normal functions");
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s.addText("Positive symptoms respond well to antipsychotic therapy (D2 blockade)", { x: 0.3, y: 1.32, w: 9.4, h: 0.46, fontSize: 14, bold: true, color: C.white, align: "center", fontFace: "Calibri" });
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  subbullet("Auditory most common — voices commanding, commenting, or conversing (2nd or 3rd person)"),
  subbullet("Visual, olfactory, tactile also possible"),
  bullet("DELUSIONS", 0, true),
  subbullet("Persecutory (most common), grandiose, referential, somatic, nihilistic"),
  subbullet("Delusions of thought insertion, thought withdrawal, thought broadcasting"),
  subbullet("Ideas of reference — neutral events perceived as personally significant"),
  bullet("DISORGANIZED THINKING / FORMAL THOUGHT DISORDER", 0, true),
  subbullet("Loose associations (derailment), tangentiality, circumstantiality"),
  subbullet("Word salad (incoherence) in severe cases"),
  bullet("DISORGANIZED / ABNORMAL MOTOR BEHAVIOR", 0, true),
  subbullet("Catatonia: stupor, waxy flexibility, mutism, stereotypy, echopraxia"),
  subbullet("Agitation, bizarre posturing"),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 8 — NEGATIVE & COGNITIVE SYMPTOMS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Negative & Cognitive Symptoms", "Often more disabling — poor response to current treatments");

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s.addText("Negative Symptoms (5 A's)", { x: 0.3, y: 1.3, w: 4.5, h: 0.45, fontSize: 14, bold: true, color: C.white, align: "center", fill: { color: C.red }, fontFace: "Calibri" });
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  bullet("Alogia — poverty of speech/thought content", 0, false),
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  bullet("Anhedonia — inability to experience pleasure", 0, false),
  bullet("Asociality — social withdrawal, reduced relationships", 0, false),
  { text: "", options: { breakLine: true, fontSize: 12 } },
  bullet("Predominate in ~1/3 of patients", 0, false),
  bullet("Associated with POOR long-term prognosis", 0, false),
  bullet("Poor response to antipsychotic therapy", 0, false),
  bullet("Related to DA hypofunction in PFC", 0, false),
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s.addText([
  bullet("Processing speed — slowed", 0, false),
  bullet("Working memory — impaired", 0, false),
  bullet("Attention / vigilance — deficits", 0, false),
  bullet("Verbal learning & memory — reduced", 0, false),
  bullet("Visual learning — impaired", 0, false),
  bullet("Reasoning & problem solving", 0, false),
  bullet("Social cognition — emotion recognition deficits", 0, false),
  { text: "", options: { breakLine: true, fontSize: 12 } },
  bullet("Present in 75–85% of patients", 0, false),
  bullet("Best predictor of functional outcome", 0, false),
  bullet("MATRICS battery used for cognitive assessment", 0, false),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 9 — DSM-5-TR DIAGNOSTIC CRITERIA
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "DSM-5-TR Diagnostic Criteria", "American Psychiatric Association, 2022");
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s.addText("CRITERION A", { x: 0.5, y: 1.45, w: 2.5, h: 0.35, fontSize: 14, bold: true, color: C.teal, fontFace: "Calibri" });
s.addText("≥2 of the following for ≥1 month (at least 1 from items 1–3):", { x: 0.5, y: 1.45, w: 9.0, h: 0.35, fontSize: 13, color: C.text, fontFace: "Calibri", align: "right" });
s.addText([
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  { text: "2. Hallucinations   ", options: { bold: true, color: C.teal, fontFace: "Calibri", fontSize: 14 } },
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  { text: "4. Grossly disorganized/catatonic behavior   ", options: { bold: false, color: C.text, fontFace: "Calibri", fontSize: 14 } },
  { text: "5. Negative symptoms", options: { bold: false, color: C.text, fontFace: "Calibri", fontSize: 14 } },
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s.addText([
  bullet("CRITERION B — Social/occupational dysfunction ≥1 major area (work, relationships, self-care)", 0, true),
  bullet("CRITERION C — Duration: Continuous signs for ≥6 months (including ≥1 month of Criterion A symptoms)", 0, true),
  bullet("CRITERION D — Schizoaffective and mood disorder exclusion", 0, true),
  bullet("CRITERION E — Substance/medical condition exclusion", 0, true),
  bullet("CRITERION F — Relationship to autism spectrum disorder excluded", 0, true),
  { text: "", options: { breakLine: true, fontSize: 10 } },
  { text: "Note: ", options: { bold: true, color: C.accent, fontSize: 13, fontFace: "Calibri" } },
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 10 — DIFFERENTIAL DIAGNOSIS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Differential Diagnosis", "Exclusion is key — diagnosis is principally one of exclusion");

const ddxData = [
  ["Category", "Conditions to Exclude", "Key Differentiator"],
  ["Psychiatric", "Schizoaffective, Bipolar I (psychotic), MDD with psychosis", "Duration & mood symptom prominence"],
  ["Brief/Spectrum", "Schizophreniform (<6 mo), Brief Psychotic (<1 mo), Delusional Disorder", "Duration criteria"],
  ["Substance-Induced", "Stimulants, cannabis, PCP, LSD, corticosteroids, L-DOPA", "Temporal link to substance use/withdrawal"],
  ["Neurological", "Temporal lobe epilepsy, Huntington's, Wilson's, Prion disease, dementia", "Neurological exam, EEG, neuroimaging"],
  ["Autoimmune/Metabolic", "Anti-NMDAR encephalitis, anti-LGI1, SLE CNS, Hashimoto's encephalopathy", "Antibody panels, CSF analysis"],
  ["Medical/Endocrine", "Thyroid disease, Cushing's, porphyria, heavy metal toxicity", "Lab workup, thyroid function"],
];
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 11 — SUBTYPES & RELATED DISORDERS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Subtypes & Related Psychotic Disorders", "DSM-5 eliminated classic subtypes; spectrum approach now used");
s.addText([
  bullet("NOTE: DSM-5 eliminated traditional subtypes (paranoid, hebephrenic, catatonic, undifferentiated) due to poor reliability & validity", 0, true),
  { text: "", options: { breakLine: true, fontSize: 10 } },
  bullet("SCHIZOPHRENIA SPECTRUM INCLUDES:", 0, true),
  subbullet("Schizotypal Personality Disorder — lifelong pattern of eccentric behavior, mild perceptual distortions"),
  subbullet("Delusional Disorder — ≥1 month delusions, no other prominent psychotic features"),
  subbullet("Brief Psychotic Disorder — sudden onset, <1 month, full remission"),
  subbullet("Schizophreniform Disorder — meets symptom criteria but 1–6 months duration"),
  subbullet("Schizoaffective Disorder — schizophrenia symptoms + independent mood disorder episodes"),
  subbullet("Substance/Medication-Induced Psychotic Disorder"),
  subbullet("Psychotic Disorder Due to Another Medical Condition"),
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  bullet("Catatonia: now recognized as a separate specifier that can occur in multiple disorders", 0, false),
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 12 — COURSE & PROGNOSIS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Course & Prognosis", "Highly variable — but early intervention improves outcomes");
s.addText([
  bullet("COURSE PHASES:", 0, true),
  subbullet("Premorbid phase → Prodromal phase (months–years) → Acute psychosis → Residual phase"),
  bullet("GOOD PROGNOSTIC FACTORS:", 0, true),
  subbullet("Acute onset, older age of onset, female sex, married/socially supported"),
  subbullet("Prominent affective symptoms, good premorbid functioning"),
  subbullet("Rapid treatment response, few negative symptoms, no family history"),
  bullet("POOR PROGNOSTIC FACTORS:", 0, true),
  subbullet("Insidious onset, early age of onset, male sex, prominent negative symptoms"),
  subbullet("Poor social support, substance use comorbidity, treatment non-adherence"),
  subbullet("Duration of Untreated Psychosis (DUP) >1 year"),
  bullet("~10% of patients die by suicide; depression is a major contributor", 0, true),
  bullet("Positive symptoms tend to attenuate with age; negative symptoms often persist", 0, false),
  bullet("Permanent full remission without recurrence occasionally occurs (rare)", 0, false),
], { x: 0.4, y: 1.3, w: 9.2, h: 4.1, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 13 — PHARMACOTHERAPY: FGA
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Pharmacotherapy: First-Generation Antipsychotics (FGAs)", "Typical Antipsychotics — D2 Receptor Antagonists");
const fgaData = [
  ["Drug", "Daily Dose (mg)", "Sedation", "Key Adverse Effects"],
  ["Chlorpromazine (low potency)", "100–1000", "+++", "Anticholinergic, orthostasis, photosensitivity, QT prolongation, cholestasis"],
  ["Thioridazine (low potency)", "100–600", "+++", "High anticholinergic; risk of retinal pigmentation, QT prolongation"],
  ["Trifluoperazine (mid)", "2–50", "++", "Well tolerated; fewer anticholinergic effects"],
  ["Perphenazine (mid)", "4–64", "++", "Fewer EPS than high-potency agents"],
  ["Haloperidol (high potency)", "1–40", "+", "HIGH EPS risk; akathisia, dystonia, NMS; less sedation"],
  ["Fluphenazine (high potency)", "1–40", "+", "High EPS; available as depot formulation"],
  ["Droperidol (high potency)", "Parenteral", "+", "QT prolongation; used for acute agitation"],
];
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  border: { type: "solid", color: C.lightGray, pt: 1 },
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s.addText("All FGAs effective for positive symptoms; NOT effective for negative/cognitive symptoms. High EPS and tardive dyskinesia risk.", {
  x: 0.3, y: 5.2, w: 9.4, h: 0.3, fontSize: 11, italic: true, color: C.subText, fontFace: "Calibri",
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 14 — PHARMACOTHERAPY: SGA
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Pharmacotherapy: Second-Generation Antipsychotics (SGAs)", "Atypical Antipsychotics — Preferred First-Line Agents");
const sgaData = [
  ["Drug", "Daily Dose (mg)", "Key Features / Notable Side Effects"],
  ["Clozapine", "150–600", "Gold standard for TRS; agranulocytosis (1%), weight gain, seizures, hypersalivation — MANDATORY CBC monitoring"],
  ["Risperidone", "2–8", "Most D2-selective SGA; elevated prolactin, EPS at higher doses; available as LAI"],
  ["Olanzapine", "10–20", "Effective; significant weight gain, metabolic syndrome, sedation; LAI available"],
  ["Quetiapine", "150–800", "Sedating; used for anxiety/insomnia; low EPS; QT prolongation risk"],
  ["Ziprasidone", "80–160", "Weight-neutral; QT prolongation — take with food"],
  ["Aripiprazole", "10–30", "Partial D2 agonist; low metabolic risk; akathisia; LAI available"],
  ["Lurasidone", "40–160", "Good metabolic profile; effective for cognitive symptoms; take with food"],
  ["Paliperidone", "3–12", "Active metabolite of risperidone; long-acting injectable available (monthly, 3-monthly, 6-monthly)"],
  ["Asenapine", "10–20", "Sublingual; moderate metabolic effects"],
  ["Brexpiprazole", "2–4", "Serotonin-dopamine activity modulator; low weight gain"],
];
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  fill: C.white,
  border: { type: "solid", color: C.lightGray, pt: 1 },
  colW: [2.0, 1.7, 5.7],
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 15 — TREATMENT-RESISTANT SCHIZOPHRENIA & CLOZAPINE
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Treatment-Resistant Schizophrenia (TRS) & Clozapine", "NICE 2025 & APA: clozapine is the evidence-based standard for TRS");
s.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.3, w: 9.4, h: 0.7, fill: { color: C.accent }, line: { color: C.accent }, rectRadius: 0.1 });
s.addText("TRS Definition: Failure to respond to ≥2 adequate trials of different antipsychotics (including ≥1 SGA) at therapeutic doses for ≥6 weeks each", {
  x: 0.4, y: 1.33, w: 9.2, h: 0.6, fontSize: 13.5, bold: true, color: C.white, fontFace: "Calibri",
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s.addText([
  bullet("~30% of patients with schizophrenia have TRS", 0, false),
  bullet("CLOZAPINE: Only antipsychotic with proven efficacy in TRS (Lancet Psychiatry 2025 meta-analysis, PMID 40023172)", 0, true),
  subbullet("Superior to all other SGAs in TRS — Schneider-Thoma et al., Lancet Psychiatry Apr 2025"),
  subbullet("Also reduces suicidality; may reduce violence"),
  bullet("CLOZAPINE MONITORING REQUIREMENTS:", 0, true),
  subbullet("Mandatory CBC: weekly × 26 wks → every 2 wks × 26 wks → monthly thereafter"),
  subbullet("Risk of agranulocytosis (~1%); neutropenia monitoring is mandatory"),
  subbullet("Clozapine myocarditis: early surveillance with troponin/CRP (Br J Psychiatry 2026 consensus, PMID 40452212)"),
  subbullet("Clozapine serum levels: target 350–600 ng/mL; >1000 ng/mL toxic"),
  bullet("Augmentation strategies for partial TRS response:", 0, false),
  subbullet("Add amisulpride, aripiprazole, or valproate; ECT may be considered"),
], { x: 0.4, y: 2.1, w: 9.2, h: 3.35, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 16 — LONG-ACTING INJECTABLES
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Long-Acting Injectable Antipsychotics (LAIs)", "Key strategy for adherence and relapse prevention");
s.addText([
  bullet("RATIONALE: Poor medication adherence is the leading cause of relapse in schizophrenia", 0, true),
  subbullet("Non-adherence within 1 year: ~50% of patients"),
  subbullet("Each relapse associated with further neurobiological deterioration"),
  bullet("NICE 2025 recommends: Offer LAI if patient prefers it or if non-adherence is a concern — do not restrict to 'refractory' cases only", 0, true),
  bullet("APA Guideline: Discuss LAI early in treatment — not just as a 'last resort'", 0, true),
  { text: "", options: { breakLine: true, fontSize: 10 } },
  bullet("AVAILABLE LAI FORMULATIONS:", 0, true),
  subbullet("Haloperidol decanoate (monthly IM)"),
  subbullet("Fluphenazine decanoate (every 2–4 weeks)"),
  subbullet("Risperidone microspheres (every 2 weeks, deltoid/gluteal)"),
  subbullet("Paliperidone palmitate: monthly (Invega Sustenna), 3-monthly (Invega Trinza), 6-monthly (Invega Hafyera)"),
  subbullet("Aripiprazole monohydrate (Abilify Maintena) — monthly; Aripiprazole lauroxil (Aristada) — monthly to every 2 months"),
  subbullet("Olanzapine pamoate (Zyprexa Relprevv) — monthly; post-injection monitoring 3 hrs required"),
], { x: 0.4, y: 1.3, w: 9.2, h: 4.1, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 17 — SIDE EFFECT MANAGEMENT
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Side Effect Management", "A major driver of non-adherence — monitor proactively");
const seData = [
  ["Side Effect", "Antipsychotic(s)", "Management"],
  ["EPS: Acute Dystonia", "FGAs > SGAs", "Benztropine or diphenhydramine IM/IV (rapid relief)"],
  ["EPS: Parkinsonism", "FGAs, risperidone", "Dose reduction; add anticholinergic (benztropine); switch to SGA"],
  ["Akathisia", "FGAs, aripiprazole", "Propranolol, benzodiazepine, mirtazapine; dose reduction"],
  ["Tardive Dyskinesia", "Chronic antipsychotics", "Valbenazine or deutetrabenazine (VMAT2 inhibitors); minimize dose"],
  ["NMS", "Any antipsychotic (rare)", "STOP antipsychotic; ICU; dantrolene, bromocriptine, lorazepam"],
  ["Weight Gain/Metabolic", "Olanzapine, clozapine, quetiapine", "Metformin (updated meta-analysis 2025, PMID 39509416); lifestyle; switch drug"],
  ["Hyperprolactinemia", "FGAs, risperidone, amisulpride", "Switch to aripiprazole (prolactin-sparing) or add aripiprazole"],
  ["Agranulocytosis", "Clozapine", "Mandatory CBC monitoring; STOP if ANC <1000/μL"],
  ["QT Prolongation", "Ziprasidone, haloperidol, droperidol", "Baseline ECG; avoid concurrent QT-prolonging drugs; electrolyte monitoring"],
];
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  border: { type: "solid", color: C.lightGray, pt: 1 },
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 18 — NON-PHARMACOLOGICAL INTERVENTIONS
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Psychosocial & Non-Pharmacological Interventions", "APA & NICE: evidence-based — not optional add-ons");
s.addText([
  bullet("COGNITIVE BEHAVIOURAL THERAPY FOR PSYCHOSIS (CBTp) — RECOMMENDED by APA & NICE", 0, true),
  subbullet("Targets hallucinations, delusions, and negative symptoms; improves insight & functioning"),
  subbullet("NICE 2025: offer to all patients, including first episode"),
  bullet("FAMILY INTERVENTION / PSYCHOEDUCATION", 0, true),
  subbullet("Reduces relapse rates by ~50% in high-expressed-emotion households"),
  subbullet("APA: recommend both patient and family psychoeducation for all patients"),
  bullet("COORDINATED SPECIALTY CARE (CSC) — APA recommends for First Episode Psychosis", 0, true),
  subbullet("Multidisciplinary team: psychiatry, psychology, social work, employment, family support"),
  subbullet("Early Psychosis Intervention (EPI) programs reduce DUP and improve outcomes"),
  bullet("SUPPORTED EMPLOYMENT (Individual Placement and Support — IPS)", 0, true),
  subbullet("Competitive employment with ongoing support; superior to prevocational training"),
  bullet("ASSERTIVE COMMUNITY TREATMENT (ACT)", 0, false),
  subbullet("Mobile, intensive outreach for high-risk patients — reduces hospitalizations"),
  bullet("COGNITIVE REMEDIATION — improves cognitive deficits; best combined with vocational rehab", 0, false),
  bullet("SOCIAL SKILLS TRAINING, PEER SUPPORT — NICE 2025 recommends", 0, false),
], { x: 0.4, y: 1.3, w: 9.2, h: 4.1, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 19 — RECENT GUIDELINES: NICE 2025
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Recent Guidelines: NICE CG178 (2025 Update)", "Psychosis & Schizophrenia in Adults — National Institute for Health & Care Excellence");
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s.addShape(pres.ShapeType.roundRect, { x: 5.1, y: 1.3, w: 4.5, h: 4.1, fill: { color: C.white }, line: { color: C.green, width: 2 }, rectRadius: 0.1 });
s.addText("NICE 2025 — Key Pharmacological Recommendations", { x: 0.3, y: 1.3, w: 4.5, h: 0.5, fontSize: 12, bold: true, color: C.teal, align: "center", fontFace: "Calibri" });
s.addText("NICE 2025 — Psychosocial Recommendations", { x: 5.1, y: 1.3, w: 4.5, h: 0.5, fontSize: 12, bold: true, color: C.green, align: "center", fontFace: "Calibri" });
s.addText([
  bullet("Offer oral antipsychotic to all patients with first episode psychosis", 0, false),
  bullet("Choose drug jointly — discuss benefits and harms including metabolic, EPS, and prolactin effects", 0, false),
  bullet("Start low, titrate slowly — especially in first episode", 0, false),
  bullet("Offer LAI if preferred OR if non-adherence is a concern", 0, false),
  bullet("Clozapine: offer after ≥2 adequate antipsychotic trials have failed", 0, false),
  bullet("Monitor physical health: weight, BMI, glucose, lipids, BP, ECG at baseline and regularly", 0, false),
  bullet("Review antipsychotic annually; document reason for continuing", 0, false),
  bullet("ECT: consider for catatonia or severe depression with schizophrenia", 0, false),
], { x: 0.4, y: 1.88, w: 4.3, h: 3.42, valign: "top" });
s.addText([
  bullet("Offer CBTp to all patients — including first episode", 0, false),
  bullet("Offer family intervention where family is in regular contact", 0, false),
  bullet("Early Intervention in Psychosis (EIP) services for ≥3 years", 0, false),
  bullet("Support peer support and self-management strategies", 0, false),
  bullet("Address physical health: smoking cessation, exercise, diet", 0, false),
  bullet("Assess and support carers' own mental and physical health needs", 0, false),
  bullet("Consider supported employment (IPS) for all working-age patients", 0, false),
  bullet("Culture, ethnicity, and race: tailor care and avoid bias in assessment", 0, false),
], { x: 5.2, y: 1.88, w: 4.3, h: 3.42, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 20 — APA & VA/DOD GUIDELINES
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "APA Guidelines (2020) & VA/DoD CPG (2023)", "American Psychiatric Association & Dept. of Veterans Affairs");
s.addText([
  bullet("APA PRACTICE GUIDELINE FOR SCHIZOPHRENIA (3rd Ed, 2020):", 0, true),
  subbullet("Recommends antipsychotic therapy for all acute and maintenance phases"),
  subbullet("Prefers SGAs over FGAs for first-line therapy due to better tolerability"),
  subbullet("Recommends CBTp, psychoeducation, supported employment (IPS), and assertive community treatment"),
  subbullet("Coordinated Specialty Care (CSC) for first episode psychosis"),
  subbullet("Side effect monitoring: metabolic, EPS, prolactin, cardiac — at regular intervals"),
  subbullet("Smoking cessation support for all patients (tobacco use disorder highly prevalent)"),
  { text: "", options: { breakLine: true, fontSize: 10 } },
  bullet("VA/DoD CLINICAL PRACTICE GUIDELINE FOR FIRST-EPISODE PSYCHOSIS & SCHIZOPHRENIA (April 2023):", 0, true),
  subbullet("Emphasizes early identification and minimizing DUP"),
  subbullet("Strong recommendation for CSC in first episode psychosis"),
  subbullet("Regular monitoring of metabolic and cardiometabolic risk"),
  subbullet("Encourages shared decision-making in antipsychotic choice"),
  subbullet("Addresses social determinants: housing, substance use, trauma-informed care"),
  bullet("Both guidelines align: treat early, monitor broadly, integrate psychosocial care", 0, true),
], { x: 0.4, y: 1.3, w: 9.2, h: 4.1, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 21 — RECENT EVIDENCE 2024–2026
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Recent Evidence (2024–2026)", "Key PubMed publications updating clinical practice");
const pubData = [
  ["PMID", "Journal / Year", "Finding"],
  ["40023172", "Lancet Psychiatry, Apr 2025", "Clozapine vs SGAs in TRS: IPD meta-analysis confirms clozapine superiority for treatment-resistant schizophrenia"],
  ["40332874", "JAMA Psychiatry, Jul 2025", "Acute-phase antipsychotic treatment: IPD meta-analysis — comparable efficacy between agents; tolerability differs"],
  ["39509416", "Schizophr Bull, May 2025", "Metformin for antipsychotic-induced weight gain: optimal dosing ≥1000 mg/day for ≥16 weeks is most effective"],
  ["39424931", "Mol Psychiatry, Mar 2025", "Umbrella review: schizophrenia patients have markedly elevated rates of cardiovascular, metabolic & respiratory comorbidities"],
  ["41058236", "Am J Psychiatry, Nov 2025", "Relapse in schizophrenia: systematic review — consensus international criteria for relapse proposed to standardize research"],
  ["40452212", "Br J Psychiatry, Apr 2026", "Clozapine-associated myocarditis: multidisciplinary consensus on prevention, monitoring & rechallenge protocol"],
  ["40042836", "JAMA Psychiatry, May 2025", "Blood leukocyte subpopulations in schizophrenia — meta-analysis: inflammatory biomarkers as potential diagnostic/prognostic markers"],
];
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  border: { type: "solid", color: C.lightGray, pt: 1 },
  colW: [1.2, 2.2, 6.0],
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// ══════════════════════════════════════════════════════════════
// SLIDE 22 — SPECIAL POPULATIONS
// ══════════════════════════════════════════════════════════════
s = pres.addSlide();
s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Special Populations & Comorbidities", "Tailored care is essential");
s.addText([
  bullet("FIRST-EPISODE PSYCHOSIS (FEP)", 0, true),
  subbullet("Use lowest effective dose; SGAs preferred; longer time needed to assess response"),
  subbullet("CSC/EIP program for at least 2–3 years (APA, NICE, VA/DoD)"),
  bullet("PREGNANCY & POSTPARTUM", 0, true),
  subbullet("Risk of relapse with discontinuation > teratogenicity risk of most SGAs"),
  subbullet("Avoid valproate; quetiapine and olanzapine relatively better studied"),
  subbullet("Monitor for neonatal EPS if antipsychotic used near delivery"),
  bullet("ELDERLY PATIENTS", 0, true),
  subbullet("Lower doses; high sensitivity to EPS, orthostasis, anticholinergic effects, cognitive impairment"),
  subbullet("Avoid high-potency FGAs; prefer low-dose SGAs (risperidone, quetiapine)"),
  bullet("SUBSTANCE USE COMORBIDITY", 0, true),
  subbullet("Cannabis use worsens outcomes — strongly advise cessation"),
  subbullet("Clozapine may reduce substance use cravings"),
  bullet("CARDIOVASCULAR / METABOLIC COMORBIDITY (Mol Psychiatry 2025, PMID 39424931)", 0, true),
  subbullet("2x increased risk of cardiovascular disease; 3x diabetes risk"),
  subbullet("Regular screening: fasting glucose, lipids, BMI, BP, smoking status"),
], { x: 0.4, y: 1.3, w: 9.2, h: 4.1, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 23 — MONITORING & FOLLOW-UP
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Monitoring & Follow-Up", "Systematic physical health monitoring is a guideline requirement");
const monData = [
  ["Parameter", "Baseline", "4–6 Weeks", "3 Months", "6 Months", "Annually"],
  ["Weight / BMI", "✓", "✓", "✓", "✓", "✓"],
  ["Fasting Glucose / HbA1c", "✓", "", "✓", "", "✓"],
  ["Fasting Lipid Profile", "✓", "", "✓", "", "✓"],
  ["Blood Pressure", "✓", "✓", "✓", "✓", "✓"],
  ["ECG (QTc)", "✓", "If indicated", "", "", "If risk"],
  ["FBC (CBC)", "✓ (all); weekly (clozapine)", "Clozapine: weekly", "Clozapine", "Clozapine → 2-wkly", "✓"],
  ["Prolactin", "✓", "", "If symptomatic", "", "✓"],
  ["EPS / AIMS (tardive dyskinesia)", "✓", "✓", "✓", "✓", "✓"],
  ["Mental State / Suicide Risk", "✓", "✓", "✓", "✓", "✓"],
  ["Substance Use Screen", "✓", "", "", "", "✓"],
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addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 24 — ACUTE AGITATION MANAGEMENT
// ══════════════════════════════════════════════════════════════
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s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.offWhite } });
addSectionTitle(s, "Management of Acute Psychosis & Agitation", "Stabilization, safety, and de-escalation first");
s.addText([
  bullet("FIRST-LINE: De-escalation techniques, safe environment, verbal de-escalation", 0, true),
  bullet("ORAL MEDICATION (if accepted):", 0, true),
  subbullet("Olanzapine 10 mg PO or Risperidone 2 mg PO + lorazepam 1–2 mg"),
  subbullet("Haloperidol 5 mg PO + promethazine 25 mg (IM combination also used)"),
  bullet("PARENTERAL (if oral refused / imminent danger):", 0, true),
  subbullet("Haloperidol 5 mg IM + lorazepam 2 mg IM (most widely used)"),
  subbullet("Olanzapine 10 mg IM — do NOT combine with IM lorazepam (respiratory depression risk)"),
  subbullet("Droperidol 5–10 mg IM — monitor QTc"),
  subbullet("Midazolam IM for extreme agitation (rapid onset)"),
  bullet("NICE 2025: violence/aggression — de-escalation first; rapid tranquillisation only if imminent risk", 0, true),
  bullet("Post-incident review and switch to oral/LAI regimen as soon as possible", 0, false),
  bullet("ECT: consider for catatonia, severe affective component, or medication-refractory agitation", 0, false),
], { x: 0.4, y: 1.3, w: 9.2, h: 4.1, valign: "top" });
addFooter(s);

// ══════════════════════════════════════════════════════════════
// SLIDE 25 — EMERGING THERAPIES
// ══════════════════════════════════════════════════════════════
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addSectionTitle(s, "Emerging & Novel Therapies", "Beyond dopamine — the next generation of treatments");
s.addText([
  bullet("MUSCARINIC AGONISTS (Xanomeline-Trospium / KarXT — FDA approved 2024):", 0, true),
  subbullet("First novel mechanism in decades — M1/M4 muscarinic agonism"),
  subbullet("Effective for positive & negative symptoms without D2 blockade"),
  subbullet("Avoids traditional EPS, weight gain, and prolactin side effects"),
  subbullet("FDA approved September 2024 — a landmark in schizophrenia pharmacology"),
  bullet("GLUTAMATE MODULATORS:", 0, true),
  subbullet("mGlu2/3 agonists (pomaglumetad) — mixed results in trials"),
  subbullet("D-serine, glycine augmentation — NMDA co-agonism for negative/cognitive symptoms"),
  bullet("TRACE AMINE-ASSOCIATED RECEPTOR 1 (TAAR1) AGONISTS:", 0, true),
  subbullet("Ulotaront (SEP-363856) — phase 3 trials; non-D2 mechanism"),
  bullet("NEUROMODULATION:", 0, true),
  subbullet("Transcranial Magnetic Stimulation (TMS) — rTMS for auditory hallucinations"),
  subbullet("ECT — still used in catatonia and TRS with affective features"),
  bullet("DIGITAL THERAPEUTICS: Apps for symptom monitoring, CBTp delivery, adherence support", 0, false),
  bullet("ANTI-INFLAMMATORY APPROACHES: COX-2 inhibitors (celecoxib), omega-3 FA — adjunctive trials ongoing", 0, false),
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// SLIDE 26 — SUICIDE & SAFETY
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addSectionTitle(s, "Suicide Risk & Safety in Schizophrenia", "~10% lifetime suicide mortality — highest risk in early illness");
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  bullet("RISK FACTORS FOR SUICIDE IN SCHIZOPHRENIA:", 0, true),
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  subbullet("Comorbid depression, insight into illness with hopelessness"),
  subbullet("Auditory command hallucinations, persecutory delusions"),
  subbullet("Substance use disorder, social isolation, unemployment"),
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  subbullet("Good medication adherence, clozapine (specifically anti-suicidal — FDA-approved for this)"),
  subbullet("Strong social support, religious beliefs, engagement with care"),
  bullet("ASSESSMENT: Routine validated screening — Columbia Suicide Severity Rating Scale (C-SSRS)", 0, true),
  bullet("MANAGEMENT:", 0, true),
  subbullet("Crisis plan, remove means, safety network, crisis team involvement"),
  subbullet("Clozapine indicated when suicidality persists despite other treatments"),
  subbullet("Inpatient admission if imminent risk"),
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// SLIDE 27 — KEY TAKEAWAYS
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const takeaways = [
  ["1", "Schizophrenia is a chronic, heterogeneous syndrome — no pathognomonic feature; diagnosis requires ≥6 months of continuous signs with ≥1 month active symptoms."],
  ["2", "Positive symptoms respond to antipsychotics (D2 blockade); negative and cognitive symptoms are harder to treat and are the main drivers of functional disability."],
  ["3", "SGAs are first-line; choose based on the patient's individual risk profile (metabolic vs. EPS vs. prolactin). Discuss and involve the patient in the decision."],
  ["4", "Clozapine is the ONLY evidence-based treatment for TRS (Lancet Psychiatry 2025). Introduce early when 2 adequate trials fail. Mandatory CBC monitoring required."],
  ["5", "LAIs should be offered early — not just as a last resort. They are the most reliable strategy against relapse driven by non-adherence."],
  ["6", "Psychosocial interventions (CBTp, family therapy, CSC, IPS) are guideline-required — not optional. Integrate from day one."],
  ["7", "Monitor physical health systematically: metabolic, cardiac, prolactin, and EPS — at baseline and regularly. Schizophrenia dramatically increases cardiovascular risk."],
  ["8", "KarXT (xanomeline-trospium) — FDA approved 2024 — is a landmark: first non-D2 mechanism drug for schizophrenia in decades."],
];
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// SLIDE 28 — REFERENCES
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  { text: "Textbooks & Guidelines\n", options: { bold: true, fontSize: 14, color: C.teal, fontFace: "Calibri", breakLine: true } },
  { text: "1. Harrison's Principles of Internal Medicine 22E (2025), Chapter 463 — Schizophrenia\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "2. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14E — Antipsychotic Pharmacology\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "3. Adams & Victor's Principles of Neurology 12E — Schizophrenia Chapter\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "4. NICE Clinical Guideline CG178: Psychosis & Schizophrenia in Adults (updated March 2025)\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "5. APA Practice Guideline for the Treatment of Patients with Schizophrenia, 3rd Ed. (2020)\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "6. VA/DoD Clinical Practice Guideline for First Episode Psychosis & Schizophrenia (April 2023)\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "7. DSM-5-TR (APA, 2022)\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "\nKey PubMed References\n", options: { bold: true, fontSize: 14, color: C.teal, fontFace: "Calibri", breakLine: true } },
  { text: "• PMID 40023172 — Schneider-Thoma et al. Clozapine vs SGAs in TRS. Lancet Psychiatry 2025\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "• PMID 40332874 — Brandt et al. Acute antipsychotic treatment IPD meta-analysis. JAMA Psychiatry 2025\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "• PMID 39509416 — Peng et al. Metformin for antipsychotic weight gain. Schizophr Bull 2025\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "• PMID 39424931 — Lee et al. Comorbid health outcomes umbrella review. Mol Psychiatry 2025\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "• PMID 40452212 — Wagner et al. Clozapine myocarditis consensus. Br J Psychiatry 2026\n", options: { fontSize: 12, color: C.text, fontFace: "Calibri", breakLine: true } },
  { text: "• PMID 41058236 — Howes et al. Relapse criteria consensus. Am J Psychiatry 2025", options: { fontSize: 12, color: C.text, fontFace: "Calibri" } },
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