Updates

Note: Content is not peer-reviewed, does not constitute medical advice, and is provided for educational/interest purposes only.

Updates

On this page updates will be listed in reverse chronological order. 

12b. Depression and related disorders

Maternal mental health

• N=528 SSRI/SNRI exposed kids vs 2522 controls tested on the EDI in kindergarten. "We found 21.43% of children exposed in utero to SSRIs or SNRIs were at increased risk of being developmentally vulnerable in 2 or more domains (versus 16.16% of unexposed children)". Link. DOI: 10.1542/peds.2019-1157

4. Etiology

Genetics

• Heritability ≠ genetic causation: A trait can be genetically determined without heritability if there's no genetic variation for that trait (e.g., having two eyes).

• Large study and missing heritability: n=347,630. It appears that a lot of the missing heritiability problems can be resolved by looking at the whole genome. However, interestingly, this large study found lower contribution of genetics for most mental-related traits. Neuroticism (18.5%), Education attainment (34.9%), Sleep (12.5%), Smoking (17.4%) (looking at the genetic contribution supplemental table 4). This is in contrast to height that showed 70.9% whole genome heritability. Link

1. Human Nature and Well-Being

Big 5, OCEAN

• Life satisfaction correlates with low neuroticism, high extraversion, high consciousness - Link

• Women are higher on agreeableness and N - Link

Life Satisfaction

• Life events can change OCEAN: Review of N=196,256 individuals. Getting married lowers openness, new employment improves conscientiousness, and lowers neuroticism. The factors most correlating with life satisfaction are: new relationship, marriage, and new employment. Link. 

7. Risk Assessment

Suicide & Durkheim

• For the next edition, we may do a segment on Durkheim's conceptualization of suicide

• Social Regulation (Organization): Anomic Suicide: Lack of regulation; normlessness from social disruption (e.g., “I’m lost without clear societal norms”) vs Fatalistic Suicide: Excessive regulation; despair from oppressive control (e.g., “I’m trapped by society’s rigid rules”).

• Social Integration (People): Egoistic Suicide: Low integration; isolation from social ties (e.g., “I feel disconnected from society” or “No one loves me”) vs Altruistic Suicide: High integration; self-sacrifice for the group (e.g., “I’m dying for others, self-sacrifice”).

• It should be noted that Durkheim was interested in social construct and this would not cover individual psychological reason for suicide. However psychological concepts can be deduced from Durkheim. Social regulation can be viewed as individual regulation: are you disorganized and acting impulsively or are you very rational and considered all possibilities but nothing worked. Social integration can be viewed as how you feel connected/dependent/responsible for others

7. Risk Assessment

APA in 1982 in the Amicus Brief for Barefoot v. Estelle

• Limitation of violence risk assessment as described by the APA in 1982 in the Amicus Brief for Barefoot v. Estelle Link 

  • “even under the best of conditions, psychiatric predictions of long-term future dangerousness are wrong in at least two out of every three”

  • “medical knowledge has simply not advanced to the point where long-term predictions [ ] may be made with even reasonable accuracy”

  • “The unreliability of psychiatric predictions of long-term future dangerousness is by now an established fact”

  • psychiatry “permits the jury to avoid the difficult actuarial questions by seeking refuge in a medical diagnosis that provides a false aura of certainty”

  • This may also be relevant to assessment or diagnosis chapter

5. Assessment

• DSM quote on need for a thorough interview "The case formulation for any given individual should involve a careful clinical history and concise summary of the social, psychological, and biological factors that may have contributed to developing a given mental disorder. It is not sufficient to simply check off the symptoms in the diagnostic criteria to make a mental disorder diagnosis. A thorough evaluation of these criteria may assure more reliable assessment”

• DSM-II quote on not making too many diagnoses "The diagnostician, however, should not lose sight of the rule of parsimony and diagnose more conditions than are necessary to account for the clinical picture."

• PHQ-9 up to ⅔ false positive - Link

  • In a study, researchers evaluated the widely used PHQ-9 scale. 153 individuals at a psychiatric clinic received the scale and clinicians interviews. Link. DOI: 10.1186/1471-244X-12-73

• The consequence of psychiatric labels

  • The issue of ever increasing prevalence of mental illness in youth is already a concern. In a 2023 study of sixth grade students, 51.2% adopted mental health labels at some point. Furthermore, the study found that adopting such a label significantly correlated with lower self-esteem. DOI: 10.1177/00221465231175936. Link

  • "At Brown and Harvard, more than 20% of undergraduates are registered as disabled. At Amherst, that figure is 34%." Link

7. Risk Assessment

Violence and schizophrenia

• For unconventional stranger homicide (this is a much narrower group than regular murder); severe mental illness is 43.3% versus 2.4% for conventional stranger homicide (though 43.6% of larger group were intoxicated) - Link. DOI: 10.1177/00258024241255779

• Antipsychotics adherence lower risk of violence (not in the paper - this could be a confounder of adherence rather than the effect of antipsychotics) - link. DOI: 10.1016/S0140-6736(14)60379-2

• Mental illness increase risk of being subject and perpetrator of violence. Schizophrenia specifically increased risk of being perpetrator but not subject (Figure 4 B). n=250,419 large Swedish study.- link. DOI: 10.1001/jamapsychiatry.2019.4275

• 2025 - Risk factors of violence in individuals with schizophrenia/psychosis (#1 Past crime, #2 drugs, #3 suicidality, rest wasn’t significant including symptoms of psychosis) - Link. DOI: 10.1192/bjp.2024.120

• Predictors of violence (deliquency/substance use/conduct problems): Poverty didn't predict violence when controlling for "positive parenting, single mother status, divorce, or child to adult ratio". Other predictor "Higher peer deviance in later adolescence." Paper also show that while violence varies some with age, it is much more heterogenous among individuals. Link. DOI: 10.1017/S0954579414000789

4. Etiology

• A study of heritability of ADHD showed that teacher estimates indicated 69% heritability vs GWAS showing 5%. Link

• “the measurable heritability of a trait does not tell us how 'genetically inheritable' that trait is.” Link

5. Assessment

• Problem with scales like PHQ-9, GAD-7, PCL-5, too many positives - link

  • PHQ-9: False positives among positives = 65%, PCL-5 False positives among positives = 55%. Despite a 2/3 false positive rate, 86.7% of patients testing positive for the PHQ-9 are prescribed antidepressants, 42.0% of those testing negative are also prescribed antidepressants, only 5-7% of those who tested positive got referred to psychiatry/psychology. Link. DOI:10.1136/bmj.b750

  • PHQ-9: •Kroenke et al. (2001) - DOI: 10.1046/j.1525-1497.2001.016009606.x

  • GAD-7 •Spitzer et al. (2006) DOI: 10.1001/archinte.166.10.1092 

  • PCL-5 •Georgescu et al. 2024 DOI: 10.1080/20008066.2024.2333222

• Simple psych-ed (like an ADHD workshop) doubles self-perception of the disorder in healthy individuals (28% to 58%) - Link. DOI: 10.1017/S0033291725101979

7. Risk Assessment

Suicide risk assessment

• Many suicides happen rapidly. Studies show large numbers that unfold within minutes of the decision (Wyder, 2004). Rapid access to a loaded gun can turn a fleeting thought into a permanent outcome.

• 2025 UK suicide guidelines - Link

• 2025 US paper advocating for Zero Suicide and suicide risk assessments for all - Link. DOI: 10.1001/jamanetworkopen.2025.3721

• 2025 Safety planning - 80% reduction in suicide in original study, 90% increase in replication study - Link. DOI: 10.1016/j.jad.2025.04.023

• The mention of command auditory hallucination as a risk factor for suicide didn't have a reference "command auditory hallucinations may identify or even place psychotic individuals at greater risk for acute, suicidal behavior — these symptoms should be the target of immediate and aggressive characterization and treatment". Link. DOI: 10.1016/j.comppsych.2012.12.022

9. Neurocognitive disorders

2025 - APA guidelines for delirium. Link. DOI: 10.1176/appi.books.9780890428023

• APA suggests that dexmedetomidine be used rather than other sedating agents to prevent delirium in patients who are undergoing major surgery or receiving mechanical ventilation in a critical care setting.

• APA suggests that melatonin and ramelteon not be used to prevent or treat delirium.

• APA says that antipsychotics shouldn’t be used to reduce delirium but to treat acute agitation that didn’t respond to verbal de-escalation

8. Neurodevelopmental disorders

MTA study (ADHD)

• MTA study initial results vs long-term. MTA original. 

• At 3 years meds or combo are no longer better than the rest. Link. DOI: 10.1097/CHI.0b013e3180686d48

• Delinquent behavior and emerging… - At 3 years more delinquency in med group. Link. DOI: 10.1097/chi.0b013e3180686d96

• The MTA at 8 years… At 8 years meds are no better. Link. DOI: 10.1097/CHI.0b013e31819c23d0

• 2025 - “After 14 months of treatment, the children who took Ritalin every day had significantly fewer symptoms… by 36 months, that advantage had faded completely, and children in every group, including the comparison group, displayed exactly the same level of symptoms.” Link. (NYT, "Have We Been Thinking About A.D.H.D. All Wrong?")

• 2025 - Swanson MTA author “If you’re honest, you should tell kids that, look, if you’re interested in next week or next month or even the next year, this is the right treatment for you. But in the long run, you’re going to be shorter. How many kids would agree to take medication? Probably none.” Link. (NYT, "Have We Been Thinking About A.D.H.D. All Wrong?")

8. Neurodevelopmental disorders

ADHD biology

• 2025 - We have a clinical definition of A.D.H.D. that is increasingly unanchored from what we’re finding in our science.” Link. (NYT, "Have We Been Thinking About A.D.H.D. All Wrong?")

• 2025 - “the evidence for each of these A.D.H.D. biomarkers has faltered.” Link. (NYT, "Have We Been Thinking About A.D.H.D. All Wrong?")

8. Neurodevelopmental disorders

Risk of stimulants

• 29% of kids on stimulants have insomnia (vs 10% in untreated) - Link. DOI: 10.1089/cap.1999.9.157

• Longitudinal study (1998) of 492 children over 20 years. ADHD with and without stimulants and controls. Examined outcomes in terms of drug dependence in adulthood. Stimulant use associated with: Increased smoking dependence by 53%, Increased cocaine dependence by 50%. Post. Link. DOI: 10.1177/002221949803100603

• 2024 - Amphetamines x5 psychosis and mania. Link. DOI: 10.1176/appi.ajp.20230329

• 2025 - 25.3% of those prescribed stimulants reported misuse - Link. DOI: 10.1001/jamapsychiatry.2025.0054

8. Neurodevelopmental disorders

ADHD

• Stimulants don’t improve academic performance. Link. DOI: 10.1037/ccp0000725

• ADHD diagnosis on its own leads to worse outcomes. 393 ADHD adolescents matched with 393 others with similar ADHD symptoms, the ones with the diagnosis do worst. Link. DOI: 10.1001/jamanetworkopen.2022.36364

• 2024 - 23% of boys have received a diagnosis with ADHD by age 17 (number not included in the paper but calculated from Table 1). Link. DOI: 10.1080/15374416.2024.2335625

• 2025 - 93.7% adults with ADHD get treatment with meds - Link. DOI: 10.1176/appi.ajp.20240492

• Review of all treatment (meds, not meds) for ADHD. Only meds have significant evidence at 12 weeks. CBT and Neurofeedback are pretty good at medium term. Few papers and high variability. Link. DOI: 10.1016/s2215-0366(24)00360-2

• 2025 - "38% of Stanford undergraduates are registered as having a disability" mostly driven by ADHD Link (Atlantic "Accommodation Nation")

• 2025 - Methylphenidate doesn’t improve exam scores. Link. DOI: 10.1007/s00213-025-06864-1

• 2025 - Data on stimulants use in adult and adolescents in the US 2005 to 2024 (figure 2). Link

  • Adults - 1.1% in 2005, 3.1% in 2024, 181.82% increase

  • Teens - 5.0% in 2005, 5.3% in 2024

9. Neurocognitive disorders

Delirium

• 2025 - Dexmedetomidine + melatonin, best to prevent delirium. Risperidone was #2, possibly against the criticism of antipsychotics in delirium. Link. DOI: 10.1111/anae.16757

• Dexmedetomidine (Precedex) - Dexmedetomidine acts by binding to alpha2-adrenergic receptors in the brainstem, which reduces the release of norepinephrine. It's primarily known for its sedative properties. It is used for delirium. Similar to clonidine.

10. Substance-related disorders

Mechanism of action (clarification)

• Alcohol mostly affects GABA-A (but also GABA-B). BZD, Barb, Z-drugs are mostly GABA-A. Baclofen and GHB are mostly GABA-B. 

• Alcohol leads to the release of endorphins from the hypothalamus and pituitary. Endorphins activate opioid receptors. Naltrexone blocks this activation.

• Gabapentin reduces Glutamate more than activate GABA-A or GABA-B (by being Ca Channel Blocker)

• Campral is an NMDA antagonist (by being a Ca Channel Blocker)

10. Substance-related disorders

Risk of stimulants

• 2024 - Amphetamines x5 psychosis and mania. Link. DOI: 10.1176/appi.ajp.20230329

Risk of sedatives

• 2024 - Some risk of addiction with Pregabalin. Link. (BBC, "Rising deaths linked to pregabalin misuse sparks review")

• 2024 - 76,137 Benzodiazepine patients vs. matched cohort found to have increased risk of mood and substance use disorders "Our findings demonstrate a concerning association between BZD use and an increased risk of being diagnosed with various mood disorders and SUDs." Link. DOI: 10.1016/j.dadr.2024.100270

10. Substance-related disorders

Other

• 2024 - Contrary to common belief, vaping doesn't appear to have replaced smoking, but added to it - Link. DOI: 10.1016/S2468-2667(24)00183-X External Link

Antidepressants for SUD

• 265 patient w/ alcohol use dz randomized to placebo v citalopram + therapy. Citalopram did not lead to higher abstinence, but was associated with more heavy drinking days, an average of 13.02 versus 7.78 for placebo. Link. DOI: 10.1111/acer.12802

• 229 patients w/ meth use dz randomized to a placebo, sertraline, contingency management or combinations found that “participants in the sertraline-only condition provided significantly more metabolite-positive urine samples.” Link. DOI: 10.1016/j.drugalcdep.2006.03.005

10. Substance-related disorders

Self-medication model

• A 2020 review noted there is "a lack of rigorous empirical evidence is support of the self-medication model." Link. DOI: 10.1037/adb0000552

GLP-1 for alcohol use disorder

• 2025 - Review. GLP-1s "show beneficial effects on consumption, relapse, and alcohol-related morbidity", did better than naltrexone. Link. DOI: 10.1016/j.eclinm.2025.103645 

11. Schizophrenia and others thought disorders

Preventing illness

• 2025 - "No evidence that any of the investigated active interventions had a sustained and robust effect on any of the investigated outcomes, compared to control interventions." Link. DOI: 10.1038/s41380-025-02902-8

Antipsychotics

• Self-reported reasons for antipsychotic use, NHANES 2013-2018. Schizophrenia 9.6%. Bipolar 25.5%. Depression 32.3%. Insomnia 16.6%. Unspecified (psychosis/mood/anxiety) 22.2%. Aka: 90+% of antipsychotics not for schizophrenia. Link. DOI: 10.1186/s12888-020-02895-4

• SGAs cause similar tardive dyskinesia as FGAs in long term. N=28,051 followed over many years. Link. DOI: 10.1097/YCO.0b013e3282f53132

• Only 6.3% of #1 antipsychotic quetiapine is for psychosis. Post. Link. DOI: 10.1136/bmjopen-2015-010861

• 2025 - Clozapine no better than other SGAs in this system review. The review "did not provide evidence for superior efficacy of clozapine." Link. DOI: 10.1016/S2215-0366(25)00001-X 

• 2025 - Cobenfy failed as an adjunct treatment to SGAs in ARISE trial. Link.

• 2025 - Nuplazid (Pimavanserin) for negative symptoms of schizophrenia failed trial - ADVANCE-2 trial - Link. DOI: 10.1093/schbul/sbaf034

• 2025 - 10 year long study of individuals with schizophrenia continuously on LAI versus others. LAI did better and seemingly did better as time went on (in contrast to Wunderick) - Link. DOI: 10.1176/appi.ajp.20240321 

• 2025 - Data on antipsychotics use in adult and adolescents in the US 2005 to 2024 (figure 3). Link. (U.S. Population Prevalence ofPrescription Psychiatric Medication Use AmongChildren and Adolescents, 2006-2023)

  • Adults - 1.9% in 2005, 3% in 2024, 57.89% increase

  • Teens - 1.3% in 2005, 1.1% in 2024

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

11. Schizophrenia and others thought disorders

Diagnostic issues

• 2023 - Risk of getting a schizophrenia spectrum disorder after ED visit for substance use (without psychosis). Hazard ratios: amphetamine 28.4, polysubstance 18.7, Cannabis 14.3, Cocaine 13.2, Alcohol, 6.1, Other 13.3 (obviously the HR are much higher when the ED presentation included psychosis). N= 9.8M. Link. DOI: 10.1001/jamapsychiatry.2023.3582 

• 2025 - CBD & psychosis. THC +/- CBD (CBD, which is sometimes thought to maybe help psychosis/cognition/mental illness), individuals randomized with CBD had worse cognition (verbal recall) and more psychotic symptoms. Link. DOI: 10.1038/s41386-025-02175-3

• 2025 - Study of autoimmune psychosis notes, n= 164. 39% were initially misdiagnosed as primary psychosis, severe cognitive dysfunction was present in 75%, 64% were also diagnosed with catatonia. Link. DOI: 10.1016/j.schres.2025.04.024

12a. Bipolar and related disorders

Treatment

• 2025 - Swedish cohort, N=105,495. "Only lithium was associated with lower depression-related hospitalisation risk." Li was "superior" to antidepressants, antipsychotics, lamotrigine, quetiapine. Antidepressant-only treatment "was associated with increased risk of mania-related hospitalisation." Link. DOI: 10.1016/S2215-0366(24)00411-5 

• Data on mood stabilizers use in adult and adolescents in the US 2005 to 2024. Link. (U.S. Population Prevalence ofPrescription Psychiatric Medication Use AmongChildren and Adolescents, 2006-2023)

  • Adults - 1.7% in 2005, 2.6% in 2024, 52.94% increase

  • Teens - 1.0% in 2005, 0.8% in 202

  • This doesn’t take into account indication which is important to note for mood stabilizers

Diagnostic

• 2025 - Pediatric bipolar down ~90% from 2013 to 2021 - Post. Link. DOI: 10.1016/j.jaac.2024.08.008

12b. Depression and related disorders

Treatment

• Add a note that historically, antidepressants weren't always described as taking weeks to work. 

  • Kuhn's 1958 re imipramine "As a rule, the initial response was evident within 2 to 3 days". DOI: 10.1176/ajp.115.5.459

  • West and Dally's 1959 re iponiazid "Improvement took place quickly, usually around the fifth to the eighth day after treatment had been begun, but sometimes even sooner." DOI: 10.1136/bmj.1.5136.1491

• Mice study. Antidepressant may work by re-adjusting the brain. If the subject is in the bad environment, the adjustement won't work. "Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment." Link. DOI: 10.1038/mp.2015.142

• ECT barely better than anesthesia, and anesthesia had less side effects. Small study, n=28. Link. DOI:  10.1371/journal.pone.0069809

• 2025 - Meta-analysis of antidepressants RCTs. Median duraction 8 weeks, yet median duration of use in practice is 5 years. Link. DOI: 10.1016/j.amjmed.2025.04.037 

• 2025 - Meta-analysis of esketamine as adjunct found "weak" effect. Link. DOI: 10.1176/appi.ajp.20240515

• 2025 - ⅔ (62.7%) of patients with depression get treated with meds only. Link. DOI: 10.1176/appi.ajp.20240492

• 2025 - Increasing dose of antidepressant is less helpful than adding adjunct medication (venlafaxine) or psychotherapy. (this is consistent with SERT saturation data). Link. DOI: 10.1192/bjp.2025.13

• 2025 - Another study showing ketamine effects blocked by opioid blockade. Link. DOI: 10.1038/s41591-025-03800-w

• 2025 - Data on SSRI use in the US 2005 to 2024. Link. (U.S. Population Prevalence ofPrescription Psychiatric Medication Use AmongChildren and Adolescents, 2006-2023)

  • • Adults - 8% in 2005, 11.1% in 2024, 38.75% increase

12b. Depression and related disorders

Alternative medicine

• Methylfolate adjunct for depression "modest" efficacy. Link. DOI: 10.1055/a-1681-2047

Zuranolone

• Mechanism of action: GABA-A positive modulation. Metabolism: CYP3A4. Caution: with other sedatives. Indication: postpartum depression. Safety/efficacy "beyond 14 days... have not been established." Approved in 2023. Package insert. 

Pramipexole

• 2025 - N=151. Pramipexole adjunct v placebo x48 weeks. Effective: remission rate: 28% v 8%. Effective per trial but with significant side effects (including insomnia). Link. DOI: 10.1016/S2215-0366(25)00194-4

• Mechanism of action: D2, D3 agonist. (D3 agonism is also in Abilify, Cariprazine, and Buspar).. Package insert.

Side effects

• 2024 - Meta-analysis. "Antidepressant discontinuation symptoms is approximately 15%", severe symptoms was about 3%. Link. DOI: 10.1016/S2215-0366(24)00133-0 

• Suicide rate in antidepressant arm 0.12% and 0.04% in the placebo arm of antidepressant trials - Link. DOI: 10.1159/000501215

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”

13. Anxiety disorders

• Lifetime prevalence of 3x more prevalent in high income countries (5.0 v 1.6). US was #3 at 7.8%. - Post. Link. DOI: 10.1001/jamapsychiatry.2017.0056 

• Randomized trial: all participants receive Lexapro for social anxiety. Half are told it's an active placebo, half are told it's a medication. Results show a 3.6 times higher response rate in those told it's a medication. Conclusion "effects of escitalopram were markedly influenced by verbal suggestions [that] favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy". Post. Link. DOI: 10.1016/j.ebiom.2017.09.031 

• 2025 - RCT of panic disorder (though most also had depression). N=60. Sertraline + placebo v Sertraline + propranolol. Conclusion: "using propranolol alongside sertraline reduces the severity of panic attacks." Link. DOI: 10.1186/s40780-025-00466-x

15. Trauma and stress disorders

• Children in households with one natural and one stepparent are more likely to be victim of abuse“We are not talking about a small effect: preschoolers in stepparent-natural-parent homes, for example, are estimated to be 40 times as likely to become abuse statistics as like-aged children living with two natural parents (i.e., about 40 chances in 3000 vs. 1 in 3000; Figure I).” Link. DOI: 10.1016/0162-3095(85)90012-3 

• 2025 - Comparing checklists to clinical interviews, only 21% of reported trauma was true positive, (79% was false positive). For symptoms, only 34% were true positive, (65.9% were false positive). A powerful argument against checklist for PTSD. Link. DOI: 10/1089/cap.2024.0126.

17. Somatic symptom disorders

• 2025 - Review/meta-analysis non-surgical treatments for low back pain (LBP). Acute LBP (<12 weeks): NSAIDs were found to be efficacious. Exercise, steroid injections, and Tylenol were not efficacious. Chronic LBP (≥12 weeks): Exercise, chiropractor, taping, capsaicin (TRPV1 agonists), and antidepressants were efficacious. Antibiotics and anaesthetics were not efficacious. Inconclusive Evidence: Evidence for the majority of other treatments (e.g., muscle relaxants, opioids, and acupuncture) is inconclusive due to low certainty or small samples. Link. DOI: 10.1136/bmjebm-2024-112974

18. Factitious disorders and malingering

• Up to 81% of individuals intentionally withhold “medically relevant information” from providers (not malingering but relevant). Link. DOI: 10.1001/jamanetworkopen.2018.5293

19. Eating and elimination disorders

• 2023 - Review/meta-analysis pharmacotherapy for bulimia. Mentions only fluoxetine is approved and is considered first-line. No pharmacotherapy was significant at improving remission rates. Link. DOI: 10.1016/j.psychres.2023.115357

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

23. Personality disorders

• 2024 - Review/meta-analysis. For individuals with BPD, psychotropics medications were not shown to be effective whether co-pathology is present or not (low certainty evidence). Link. DOI: 10.1192/bjp.2024.172

12b. Depression and related disorders

Pediatric Depression

• 2025 - Data on SSRI use in the US 2005 to 2024. Link. (U.S. Population Prevalence ofPrescription Psychiatric Medication Use AmongChildren and Adolescents, 2006-2023)

  • • Adolescents has gone up from 1.5% 2005 to 3.6% 2024, 140% increase

• 2025 - Reanalysis of TADS study. 

  1. • Original TADS study (2004). 439 adolescents treated with Prozac, CBT, Combo, or Placebo for 12 weeks. Result combo was reportedly best, prozac alone was better to CBT alone. Response was 71 for combo, 60.6 for prozac, 43.2 for CBT, and 34.8 for placebo. Re adverse events “fluoxetine did not appear to increase suicidal ideation” but acknowledges an “excess” number of suicide attempts while adding the caveat that there may have been “imbalance across treatment groups in risk for suicide at baseline.” Link. DOI: 10.1001/jama.292.7.807

     • Reanalysis response rate: 70 combo, 62 prozac, 44 CBT, 38 placebo. Their statistics, prozac wasn’t better than placebo and there were more prozac side effects found including 9 suicide attempts in prozac arms and 1 in the no prozac arms. Link. DOI: 10.1177/09246479251337879