Olanzapine
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
Olanzapine: Benign paroxysmal torticollis of infancy
One-Sentence Summary
Olanzapine is an atypical antipsychotic originally used for schizophrenia, bipolar disorder and depressive and anxiety disorders. The TxGNN model predicts it may be effective for benign paroxysmal torticollis of infancy (highest-ranked prediction), but this is a model prediction only, with 0 clinical trials and 0 publications. The best-supported predictions for this drug are agoraphobia (open-label and case-report evidence) and neurotic depression and melancholia (systematic reviews and meta-analyses of antipsychotic augmentation), which are covered below.
Quick Overview
The top-ranked prediction has no supporting evidence, so the table shows it alongside the two best-supported alternatives.
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication (rank 1) | Benign paroxysmal torticollis of infancy |
| TxGNN Prediction Score | 0.9954 |
| Evidence Level | L5 (rank 1) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold (rank 1) |
Summary of the top 10 predictions
| Rank | Predicted Indication | Score | Evidence Level | Recommendation |
|---|---|---|---|---|
| 1 | Benign paroxysmal torticollis of infancy | 0.9954 | L5 | Hold |
| 2 | Agoraphobia | 0.9947 | L5 | Research Question |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this report. Based on known information, olanzapine is a second-generation antipsychotic whose efficacy in schizophrenia and bipolar disorder is established. Its receptor profile (5-HT2A/2C, D2 and H1 antagonism) may modulate mood and fear circuits.
Rank 1 (benign paroxysmal torticollis of infancy): Only the model score supports this. The condition is a paediatric, probably channelopathy-related migraine equivalent, and no plausible olanzapine mechanism is evident. Antipsychotic use in infants would also raise significant safety concerns.
Agoraphobia (rank 2): Agoraphobia is closely tied to panic disorder. A 12-week open-label trial of low-dose olanzapine (5 mg/day) added to an SSRI in 31 patients with SSRI-resistant panic disorder, with or without agoraphobia, supports a possible role, along with case reports. The evidence is indirect, uncontrolled and small.
Neurotic depression and melancholia (ranks 6 and 7): Both fall within the major depressive disorder spectrum, which is already an original indication for olanzapine. Several systematic reviews and network meta-analyses support antipsychotic augmentation in treatment-resistant depression, and the olanzapine-fluoxetine combination is established in this setting. No studies specific to either diagnosis were supplied.
Ranks 4, 9 and 10: These are prediction only, with no mechanistic rationale supported by the data.
Clinical Trial Evidence
Currently no related clinical trials are registered for any of the predicted indications.
Literature Evidence
No literature was found for the rank 1 prediction. The table lists the most relevant publications for the best-supported predictions, prioritised by study type.
| PMID | Year | Type | Journal | Indication | Key Findings |
|---|---|---|---|---|---|
| 34986373 | 2022 | Systematic review / network meta-analysis | J Affect Disord | Neurotic depression, melancholia | Compares augmentation agents in treatment-resistant depression |
| 34238049 | 2021 | Systematic review / meta-analysis | J Psychopharmacol | Neurotic depression, melancholia | Antidepressant plus second-generation antipsychotic vs esketamine vs lithium in treatment-resistant major depression |
| 35861202 | 2023 | Systematic review / meta-analysis | J Psychopharmacol | Neurotic depression, melancholia | Augmentation and combination treatments for early-stage treatment-resistant depression |
| 38360024 | 2024 | Systematic review / network meta-analysis | Lancet Psychiatry | Neurotic depression, melancholia | Efficacy and safety of pharmacological treatments for psychotic depression |
| 21154393 | 2010 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Dysthymic disorder | Second-generation antipsychotics in major depressive disorder and dysthymia |
| 16415705 | 2006 | Open-label trial | J Clin Psychopharmacol | Agoraphobia | Olanzapine 5 mg/day added to an SSRI for 12 weeks in 31 patients with SSRI-resistant panic disorder |
| 26635099 | 2016 | Systematic review | Expert Opin Pharmacother | Agoraphobia | Treatment-resistant panic disorder; no controlled olanzapine data |
| 40946318 | 2026 | Systematic review | Psychother Psychosom | Agoraphobia | Treatment options in treatment-resistant anxiety disorders |
| 25963405 | 2016 | Review | Asia Pac Psychiatry | Melancholia | Antipsychotics as antidepressants, effective at subantipsychotic doses |
| 10739446 | 2000 | Case report | Am J Psychiatry | Agoraphobia | Olanzapine and panic attacks |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 3381Y | APO-Olanzapine ODT | Tablet 5 mg (orally disintegrating) | Not listed in the data compiled for this report |
Safety Considerations
Contraindications and cautions (from knowledge graph disease associations, not product label text): The knowledge graph links olanzapine to cautions or contraindications in several groups of conditions:
- Metabolic: diabetes mellitus, hyperglycaemia, diabetic ketoacidosis, hyperlipidaemia, hypertriglyceridaemia, obesity
- Cardiovascular and cerebrovascular: stroke, cerebrovascular disorder, cerebral infarction, myocardial infarction, orthostatic hypotension, hypotensive disorders
- Hepatic and haematological: liver disease, cirrhosis, liver failure, gallbladder disease, neutropenia, agranulocytosis, blood coagulation disease
- Other: epilepsy, benign prostatic hyperplasia, female breast carcinoma, multiple system atrophy, postural orthostatic tachycardia syndrome
Drug interactions: 100 interactions were identified. The main ones include:
- Major: bupropion, morphine, potassium citrate
- Moderate: antidiabetic agents (acarbose, metformin, alogliptin, albiglutide, canagliflozin, dapagliflozin, chlorpropamide), anticholinergics (atropine, hyoscyamine, glycopyrronium), clarithromycin, famotidine, epinephrine, loperamide, lorcaserin, and bowel preparations
Metabolic risk is also documented in the literature, with a meta-analysis showing high rates of metabolic syndrome in people with psychotic and mood disorders (PMID 26407790). Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold for the rank 1 prediction (benign paroxysmal torticollis of infancy). Proceed with Guardrails for neurotic depression and melancholia. Agoraphobia and dysthymic disorder remain research questions.
Rationale:
- The rank 1 prediction rests only on a model score, with no trials, no literature and no plausible mechanism, and infant exposure to an antipsychotic raises safety concerns.
- Neurotic depression and melancholia fall within the depression spectrum, where antipsychotic augmentation is supported by multiple systematic reviews. However, these are indirect and not specific to olanzapine or to these diagnoses, and no registered trials were supplied. Because they overlap with an existing indication, they offer little genuinely new repurposing value.
To proceed, the following is needed:
- Mechanism of action data and the PI warnings and contraindications (not available in the data compiled for this report)
- Approved indication text for ARTG 3381Y
- Controlled trials of olanzapine in agoraphobia or panic disorder, and in dysthymia
- A metabolic, weight and sedation monitoring plan for depression and anxiety populations, limiting use to treatment-resistant cases
- Review of interaction risks, particularly with antidiabetic agents, bupropion and morphine
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.