III - Treatment

Note: Content is not peer-reviewed, does not constitute medical advice, and is provided for educational/interest purposes only.

24. Treatment Principles

•  Placebo

  • TMS v Sham TMS. VA study, n=164. No significant difference, in part due to robust sham TMS response. Remission rate TMS 40.7%, sham 37.4%. "placebo response has been increasing over time". Link. DOI: 10.1001/jamapsychiatry.2018.1483

  • 2024 - Systematic review & meta-analysis of placebo comparing effect size of placebo in different disorders. MDD and GAD had highest effect size. Link. DOI: 10.1001/jamapsychiatry.2024.0994

• Eugenics

  • Psychiatry has a terrible history of promoting eugenics (the death of our patients).

  • Maybe the largest effort in doing so was when the Nazis sterilized or killed the majority of individuals with schizophrenia in Germany. "However, postwar rates of the incidence of schizophrenia in Germany were unexpectedly high." Link. DOI: 10.1093/schbul/sbp097

25. Psychotherapies

• Will likely add a section on Behavioral therapy interventions

• Will likely add a subsection on concerns about excessive validation. Link 1, Link 2.

• 2025 - Psychodynamic "non-inferior to CBT in reducing depressive symptoms". N=290. Link. DOI: 10.1016/j.jad.2024.10.122

• 2024 - N-1649 VA study showing that what is considered "adequate" therapy is often too short to be effective. Link. DOI: 10.1037/ser0000830 

• Consumer Report survey of mental health in 7,000 subscribers. Link. DOI: 10.1037/0003-066X.50.12.965

  • 2,900 saw mental health professionals. 426 felt “very poor” prior to treatment, 87% of those improved. Among the 786 who felt “fairly poor”, 92% improved. The longer the treatment the more improvement subscribers had, measured up to more than two years.

  • “There was no difference between psychotherapy alone and psychotherapy plus medication for any disorder.” 

  • “psychologists, psychiatrists, and social workers did equally well”

  • “Alcoholics Anonymous (AA) did especially well… significantly bettering mental health professionals.”

  • “all forms of psychotherapies do about equally well”

26. Psychopharmacology

• Mention the possible association between Cobenfy and Nicotine. Individuals with schizophrenia are beleived to have an association with smoking. It may help them through acetylcholine agonism (like Cobenfy).

• Clozaril has M4 agonism, and norclozapine has M1 agonism. This is consistent with the drooling and may explain why Clozaril is better

  • 2025 - “Clozapine has a unique clinical pharmacology, compared to the other antipsychotics. The long-sought mechanism of action for clozapine’s distinct antipsychotic properties appears to be partial agonism at muscarinic acetylcholine receptors (M4 and possibly M1).” Link. DOI: 10.1177/02698811251319458 

• 2025 - Anticholinergic burden correlates with poor cognitive function in individuals with psychosis and ameliorates with tapering. Link. DOI: 10.1176/appi.ajp.20240260

• 2025 - Anticholinergic equivalence chart highlights. Link. DOI: 10.1097/JCP.0000000000002073

  • Contrary to common belief Hydroxyzine, Mirtazapine, Trazodone are not anticholinergic - sedation isn't equal to anticholinergic those medication are antihistamine. Quetiapine is not either (but its metabolite norquetiapine is).

  • Anticholinergic is not on-off but gradual and can be conceptualized using the anticholinergic chart.

• A common belief is that short-acting agents are more "addictive" due to the rapid on & off. However, it has long be known that this may not be the case in the long-term. In this 1990 publication of of individuals coming off Xanax and Valium. People in the Valium discontinuation group were twice as likely to have severe withdrawal. This may be due to the fact that long-acting agents are constantly saturating receptors. Link. DOI: 10.1016/0022-3956(90)90037-Q

• During our (Mark's and I) discussion on how to best visually represent IC50 & Ki of different psychotropic medications, we had a lot of concerns about what references to pick as some have differing data. This paper highlights this conundrum. Ultimately we thought that listing references for each data point best addressed this concern. "Combining IC50 or Ki Values from Different Sources Is a Source of Significant Noise". Link. DOI: 10.1021/acs.jcim.4c00049J

• Add Droperidol and Dexmedetomidine psychodynamics.

  • Could only fine Alpha 1 & 2 for dexmedetomidine Millan et al., 2000

27. Interventional psychiatry

28. Systems-based practice

28. Systems-based practice

29. Ethics and culture

30. Forensic psychiatry

31. Case Examples

##. Deprescribing (possible new chapter)

• A chapter on deprescribing would surely discuss hyperbolic tapering.

• Study on antidepressants cross-tapering with fluoxetine. Link. DOI: 10.1503/jpn.250054

  • (1) Taper Original SSRI to the lowest commercially available dose. (2) Add Fluoxetine 5 mg/day while maintaining original SRI, 60%+. (3) Discontinue Original SRI, 60%. (4) Taper Fluoxetine using weekly dosing. 

  • Example: Week 1–4: 20 mg weekly (equiv. to ~2.9 mg/day), 50%. Week 5–8: 10 mg once weekly (equiv. to ~1.4 mg/day), 40%. Week 9–12: 5 mg once weekly (equiv. to ~0.7 mg/day). 20%. Stop.

• 2026 - Review/meta-analysis of antidepressant tapering method. N=17,379 fully or partially remitted. "slow tapering plus psychological support is as effective as antidepressant continuation in preventing relapse and superior to abrupt or rapid discontinuation". Note that slow tapering without psych support wasn't clearly more effective than abprut discontinutation.

##. Other

Other medications with psychiatric effects

• 2025 - "finasteride use can cause depression and suicidality". Link. DOI: 10.4088/JCP.25nr15862

https://www.psychiatrist.com/jcp/analytical-review-depression-suicidality-finasteride/