Managing depression and psychosis: treatment-resistant depression pathway and antipsychotic care for GPs
A GP-facing summary of the depression/psychosis half of a Nova Mentis Clinic education evening — verifying true treatment resistance, SWITCH/augment/escalate options including E C T, T M S and esketamine, plus metabolic monitoring, extrapyramidal side effects, clozapine red flags and relapse prevention.
- Primary speakers
- Dr Sanoop Jacob Mammon (consultant psychiatrist, Nova Mentis Clinic) — treatment-resistant / difficult-to-treat depression, antidepressants, psychotherapy, augmentation, E C T / T M S / esketamine. Dr Kartika Johnson (consultant psychiatrist, Nova Mentis Clinic) — antipsychotic management for GPs, metabolic monitoring, E P S, clozapine, relapse prevention. Hosted by Fran (Nova Mentis).
- Session context
- Otter id
RCvSxWYhbA4_v62Qnsu6HIk9tM8· title Managing Depression and Psychosis · ~53.5 min (3213 s) · recorded 2026-09-19 (same Nova Mentis evening as the ADHD forum). ASR is imperfect — drug names and doses in Otter are often garbled; phrase cautiously and verify product info / PBS before prescribing.
Key messages for GPs
- Treatment-resistant depression (T R D): two adequate antidepressant trials in the same episode (dose + ~6–8 weeks + adherence) with inadequate response — not a week of tablets or trials across different lifetime episodes.
- Before calling it T R D, exclude pseudo-resistance: bipolarity, untreated psychosis, trauma/D V, personality drivers, substances, medical mimics, sleep/OSA, poor exposure (dose/duration/adherence/absorption/interactions).
- Psychotherapy is a mainstay (alone for mild; with/without meds for moderate; meds first-line for severe/psychotic depression).
- After two failed adequate trials, chance of a third agent working was framed as ~10% — consider specialist pathways for T M S / E C T / esketamine rather than endless cycling alone.
- GPs are central to antipsychotic metabolic monitoring, side-effect enquiry and early-warning relapse signs; do not abruptly stop or chop-change antipsychotics in primary care without a plan.
- Clozapine: constipation, hypersalivation, metabolic health, monthly bloods; fever / chest pain / SOB / persistent tachycardia / severe constipation / seizures / confusion → ED. Missed >~48–72 h: do not restart previous dose without specialist/clozapine line advice.
What counts as treatment-resistant depression
Working definition used: adequate trial of two antidepressants with inadequate response in the current episode. Adequate means therapeutic dose, about six to eight weeks, and adherence. One week at a “good” dose is not a trial. Trials from old episodes do not count toward the current-episode criterion.
Worked example that is not T R D: sertraline 10 mg for four weeks (“not working”) then venlafaxine 75 mg for three weeks, PHQ-9 still 19, nightly cannabis, no psychotherapy — dose, duration, substances and missing therapy all undermine the label.
RESET and the five-step pathway
First verify: unipolar major depression vs bipolar depression; secondary/comorbid psychosis; trauma / ongoing D V; personality factors prolonging episode; substance-induced or substance-maintained symptoms; medical contributors.
RESET mnemonic (exposure / dose / duration / adherence / absorption / interactions; sleep and somatic drivers; environment/social drivers; tracking outcomes with scales if needed):
- Exposure: dose appropriate? Duration enough? Adherent? Absorption (e.g. post-bariatric — consider levels)? Inducing drug–drug interactions lowering levels?
- Somatic: untreated O S A, chronic pain, thyroid, anaemia, B12/folate, menopause, perinatal.
- Environment: housing, work, carer burden, finances, violence at home.
- Tracking: clinical exam ± MADRS / PHQ-9 to quantify and monitor.
Then: optimise (including psychotherapy) → switch if no response after optimisation → consider augmentation if partial response at max dose → escalate for severity/complexity/procedures.
Matching antidepressants and psychotherapy
Trials show broadly similar efficacy across antidepressants; choose by symptom profile and tolerability (clinical preference still matters). Speaker preferences from the night — verify current product info:
| Clinical lean | Agents discussed | Caveats from talk |
|---|---|---|
| Anxiety / first episode | S S R I — sertraline or escitalopram preferred over fluoxetine | Fluoxetine: interactions, long half-life/washout. Expect early activation, G I (~10%), sexual dysfunction (delayed ejaculation / anorgasmia) — counsel early |
| Low energy / chronic pain | S N R I (e.g. duloxetine, venlafaxine) | Venlafaxine can raise B P — avoid defaulting when hypertension already present |
| Insomnia + low appetite | Mirtazapine | Sedation at lower doses; appetite increase persists — adherence risk if body-image sensitive |
| Cognitive symptoms / poor tolerance | Vortioxetine (Brintellix) | Not PBS-subsidised as framed; private cost ~$75/box cited |
| Reversed sleep rhythm | Agomelatine (Valdoxan) | Baseline and on-escalation L F Ts — hepatotoxicity risk; many referrals lack L F Ts |
| Older adults / polypharmacy | Escitalopram often favoured | S S R I / S N R I → S I A D H / hyponatraemia; all ADs small QTc effect |
Psychotherapy: alone for mild; ± meds for moderate; meds first-line for severe; psychotic depression needs meds (± antipsychotic). Match modality (C B T, interpersonal, trauma-informed / psychodynamic) to presentation. Refer psychology early.
Switch, augment, escalate
Older staging wanted different classes for T R D; newer framing: two adequate trials of any class can meet criteria — but clinically many still move S S R I → S N R I / agomelatine / mirtazapine rather than a second S S R I. Cross-taper with specialist input preferred if rapid; ideal is reduce ~50%, wait ~five half-lives, start next low. Australian Prescriber A3 antidepressant switching chart mentioned as a resource.
Augmentation (off-label for depression as monotherapy): low-dose antipsychotics (aripiprazole, quetiapine, olanzapine — not antipsychotic target doses); lithium (target levels framed ~0.4–0.8, lower than full bipolar); low-dose T3. T C A / M A O I and procedural treatments → specialist.
High/escalating suicide risk, psychosis, catatonia, serious self-neglect / emaciation, mania/mixed states, suspected bipolarity, complex comorbidity, need for T C A / M A O I or procedures. Referral letter: formulation + each trial’s drug, dose, duration, adherence — otherwise psychiatry restarts from scratch.
E C T, T M S, esketamine and emerging options
- E C T: most effective acute antidepressant modality framed — reserved for severe/psychotic depression, catatonia, severe suicidality or life-threatening self-neglect; cognitive effects (worse with prior M C I / cerebrovascular disease). Plan relapse-prevention meds during/after course.
- r T M S: awake, no anaesthetic; scalp discomfort, headache, facial twitching, light-headedness. Response ~50–60% cited in T R D vs ~10% third-drug chance. Medicare bulk-bill pathway discussed (age ≥18, M D D, inadequate response to two antidepressants of different classes, psychology attempted, no prior T M S) with lifetime session caps that speakers felt were too tight for recurrent T R D. Local bulk-bill options mentioned (e.g. Springwood / Robina-area practices — confirm current lists).
- Esketamine: T G A for T R D; acute suicidality / symptom bridge while oral ADs build; maintenance more specialised/hospital-adjacent. Racemic ketamine off-label discussed.
- Psychedelic-assisted therapy: regulated, few authorised prescribers, intensive psychology support, costly; psilocybin pathway for T R D mentioned as highly restricted. M D M A: T G A for treatment-resistant P T S D (not depression); private costs framed as very high (~$30k cited).
- Supplements: correct deficiencies; omega-3 (E P A-rich) some signal; St John’s wort serotonergic — serotonin syndrome risk with S S R Is; weak/mixed evidence for saffron, zinc, probiotics, S A M e.
Antipsychotics in primary care
Dr Johnson: GPs provide continuity — check what they take and how, metabolic health, early warning signs, and action against a shared crisis plan. Assess preference and smoking status (induces some APs). First-episode psychosis guidelines (2026 Great Pathway framed): prefer partial dopamine agonists (aripiprazole, brexpiprazole, cariprazine, or similar PBS-approved options — ASR garbled some names) when suitable. Review ~two weeks for tolerability/early response; consider switch by ~2–4 weeks if no/partial response or intolerable effects. Clozapine earlier rather than “last resort forever” if non-response — earlier may allow smaller effective doses.
Every review: name/dose/formulation/depot timing; “is it helping?” (insight); function and sleep; missed doses; five side-effect domains — weight, sedation, E P S, anticholinergic, sexual; red flags.
E P S, metabolic monitoring and clozapine
Metabolic monitoring: baseline before start/switch/add — weight, B M I, waist, B P, fasting or random glucose, lipids, plus F B C, U&E, L F Ts, prolactin, E C G as relevant. Early weeks: weight/waist/B P; sugars ~four weeks. Repeat bloods ~three months then annually if stable; more often if abnormal. Discuss weight, diet, exercise, metformin/other agents early — weight gain drives cessation.
| E P S type | Timing | Clues / action from talk |
|---|---|---|
| Acute dystonia | Hours | Painful sustained contractions, oculogyric crisis, torticollis, dysphagia → urgent care / E D; benztropine injection |
| Akathisia | Days–weeks | Inner restlessness, pacing; suicide risk if ignored. Reduce other contributors / lower AP / propranolol or short B Z D / switch |
| Parkinsonism | Weeks–months | Bradykinesia, rigidity, masked facies, tremor → dose review, switch, psychiatry |
| Tardive dyskinesia | Months–years | Repetitive orobuccolingual / limb movements → specialist (± neurology); clozapine consideration. Do not abruptly switch APs in primary care alone |
Fever, infection, chest pain, shortness of breath, persistent tachycardia, severe constipation / abdominal pain, seizures, confusion. Missed doses ≥2 days: do not restart prior dose — clozapine central line / psychiatrist / acute care; >72 h usually needs hospital re-titration.
Also check bowel habit (laxatives), hypersalivation coping, metabolic health, adherence to monthly bloods.
Relapse prevention and when to refer
Early warning signs (family / N D I S workers often spot first): withdrawal, reduced outings, insomnia, irritability/argumentativeness, rising self-neglect. Ask specifically about missed doses day-by-day. Ideal psychiatry letter: drug/dose/formulation/timing; target symptoms; monitoring plan; side-effect escalation triggers; who prescribes; crisis/relapse plan.
- Emergency / acute M H: immediate suicide/violence risk, severe agitation, catatonia, rapidly worsening psychosis, delirium, N M S, severe dystonia, medical instability, clozapine red flags.
- Prompt psychiatry: first-episode / new psychosis, diagnostic uncertainty, breakthrough symptoms, intolerable AEs / T D, wanting switch or L A I change, inherited polypharmacy/high-dose regimens, failed two adequate APs → consider clozapine opinion.
- Routine/annual: substance/medical complexity, pregnancy/breastfeeding, major organ comorbidity, unclear shared-care roles, patient preference for annual specialist review.
Q&A: long-term benztropine from public discharges may have been intended short-term — review need; dry mouth may improve with dose reduction; alternatives like low-dose promethazine discussed cautiously; persistent E P S may mean changing the antipsychotic, not endless anticholinergic.