Psychiatry Pearls for the Neurologist

Educational Objectives

The goal of this program is to improve management of depression and anxiety. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize demographic factors which impact use of antidepressants.
2. Evaluate efficacy of various medications for treatment of depression.
3. Differentiate among various presentations of anxiety disorders.

Summary

Depressive Disorders

Diagnosis of major depressive disorder (MDD): extensive psychiatric research shows weak association between stressful life events and diagnosis of MDD; diagnosis can be made independently of the associated psychosocial context; while psychosocial factors can influence many psychiatric diagnoses, MDD diagnosis is more tied to, eg, personality traits, neuroticism, genetic risk, disturbed family environment, low parental warmth; hence, clinicians should avoid solely attributing mood episodes to external circumstances

Antidepressant epidemiology: despite recent debates regarding overprescription, data indicate stable antidepressant use, with women more likely to take antidepressants than men; while similar use patterns exist across various age groups, cultural differences, rather than socioeconomic status, significantly impact use prevalence; increased antidepressant use correlates with overall lower suicide rates, suggesting a potential direct effect on depression reduction or improved mental healthcare; watchful waiting is reasonable early in the course of treatment of mild depression

Placebos: interact with opioid receptors; can be counteracted by naloxone; the mechanisms of action include expectancy, conditioning, and regression to the mean (ie, patients are likely to experience symptomatic improvement over time); adherence to placebos is linked to decreased mortality (the “healthy adherer effect”); a meta-analysis and systematic review found a response rate of ≈54% with antidepressants vs≈37% with placebo; managing high placebo response in pharmaceutical trials can challenge drug efficacy assessment; response to antidepressants remains consistent, while placebo response decreases, with increased severity of depression

Schneider et al (2003): demonstrated typical response rates of 45% for sertraline vs 35% for placebo among elderly outpatient individuals with major depression; medication visits and placebo accounted for ≈78% of the response among individuals taking sertraline, highlighting that the actual clinical benefit from sertraline is relatively modest, compared with placebo; antidepressants work for moderate-to-severe depression

Pharmacogenetic (PGx) testing: PGx testing helps identify cytochrome P450 enzyme variations affecting drug metabolism; study results are conflicting with regard to benefits; Perlis et al (2020) demonstrated no association with significant improvement in primary efficacy outcome; Oslin et al (2022) demonstrated reduction in prescriptions for medications with predicted drug-gene interactions, compared with usual care; the practical significance of minor changes in drug levels also remains unclear; PGx testing should not be a frontline approach but considered when patients experience unusual side effects or do not benefit from initial treatment; PGx is costly, ranging from $1500 to $2000 per test

Medication Management of Depressive Disorders

STAR*D trial (Rush et al [2004]): randomized patients with depression to different treatment levels, with level progression occurring with treatment nonresponse; level 1 therapy consisted of citalopram; with level 2 therapy, patients could switch medications or add augmentation or psychotherapy; with level 3 therapy, patients could switch to mirtazapine or nortriptyline, or opt for augmentation with lithium or triiodothyronine (T3); level 4 therapy involved switching to a monoamine oxidase inhibitor or combination therapy with venlafaxine and mirtazapine; outcomes — bupropion, sertraline, and venlafaxine were equally efficacious in patients in whom citalopram was ineffective; the remission rate was only 25%, regardless of the medication class; augmentation with bupropion showed slight superiority over augmentation with buspirone; augmentation seemed more efficacious than switching medications; with the exception of augmentation therapy with T3, remission rates with level 3 or 4 therapy were <20%

Tricyclic antidepressants: amitriptyline and imipramine undergo hepatic metabolism into less-sedating forms, compared with nortriptyline and desipramine (both of which are more preferred by the speaker to treat neuropathic pain and sleep issues)

Triiodothyronine (T3): used to augment antidepressant therapy; remission rate is ≈25%; compared with other antidepressants, T3 has a more rapid onset of action, producing noticeable symptomatic improvements within a few days to 2 wk; standard dosing may involve starting at 12.5 mcg and increasing every 2 days to a maximum dose of 50 mcg; Rush et al (2004) demonstrated more statistically significant improvement with augmentation with T3 vs lithium (≈24% vs ≈16%); T3 is ≈10-fold more potent than T4; T3, not T4, penetrates the blood-brain barrier; prolonged use of T3 may induce subclinical hyperthyroidism and increase the risk for osteoporosis with ≥1 yr of use; discontinuation of T3 does not necessarily cause relapse

Nonprescription Therapies for Depressive Disorders

Light therapy: advocated by the Center for Environmental Therapeutics, light therapy offers an affordable option for managing depression; light boxes cost ≈$200 and have shown efficacy in small clinical trials; Lam et al (2016) demonstrated the greatest response among patients with nonseasonal MDD who received a combination of fluoxetine and light therapy for 8 wk; light monotherapy also yielded positive results, outperforming fluoxetine monotherapy and placebo

Bibliotherapy: while traditional book reading has declined, the abundance of mental health apps provides accessible resources for patients

Anxiety Disorders

Relationship with cues: uncued anxiety — panic disorder is likely when uncued anxiety is accompanied by spontaneous panic attacks; isolated panic attacks, while possible, rarely lead patients to seek psychiatric care; patients with free-floating anxiety without panic attacks are likely to have generalized anxiety disorder (GAD) or obsessive-compulsive disorder (OCD); cued anxiety — anxiety triggered by social situations and fear of judgment suggests social phobia or social anxiety disorder; anxiety linked to reminders of traumatic events indicates posttraumatic stress disorder (PTSD); anxiety about places where escape might be difficult or where help may be unavailable (eg, open spaces, bridges) suggests agoraphobia; anxiety about developing a medical illness is illness anxiety disorder (IAD)

Classic natural history of panic disorder: panic attacks, characterized by acute anxiety, often involve fears of death, passing out, or losing control (ie, cognitive triad); not all episodes of acute anxiety are associated with panic attacks; panic attacks typically last for 10 to 20 min, while states of acute anxiety may have a longer duration; individuals may fear subsequent panic attacks, leading to heightened bodily awareness and distorted beliefs and avoidance of triggering situations; missing work due to, eg, avoiding public transportation indicates a dysfunction which leads to diagnosis of panic disorder; reinforcement of distorted beliefs exacerbates agoraphobia; panic attacks may also be seen with, eg, PTSD; panic disorder is characterized by the presence of recurrent, unexpected, uncued panic attacks and worry about recurrence (which leads to avoidance behaviors)

Somatic symptom disorder (SSD) vs IAD: individuals with SSD typically present with existing symptoms, whereas symptoms may be absent or mild in IAD; SSD involves disproportionate, persistent thoughts about symptom seriousness, whereas IAD involves worry about having a severe illness; though both disorders involve persistently high anxiety levels about health, easy alarming about personal health status, excessive time and energy devoted to health concerns, and excessive health-related behaviors and maladaptive avoidance, only one of those characteristics is required for diagnosis of SSD, while diagnosis with IAD requires all 4 characteristics; thus, SSD is more common than IAD; symptoms of SSD and IAD can worsen with stress; individuals with IAD may exhibit behaviors consistent with OCD which can reinforce anxiety; avoid reinforcement of maladaptive behaviors

Obsessive-compulsive disorder: though ≈80% of all individuals experience intrusive thoughts and ≈66% of all individuals experience compulsions (stereotypical or superstitious behaviors; eg, ensuring doors are closed or locked), these concerns persist and continuously bother individuals with OCD; caution is needed to avoid reinforcing reassurance-seeking behaviors about health concerns in individuals with IAD; helping patients achieve desensitization to the uncertainty of a health concern helps reduce the need for constant reassurance

Treatment of Anxiety Disorders

Psychotherapy: various forms are available, many of which are evidence-based; include, eg, cognitive-behavioral therapy, third-wave therapies (eg, mindfulness-based approaches), exposure therapy; any treatment with an exposure component is generally thought to be very effective

Pharmacologic therapy: selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatment; adjunctive treatments to SSRIs include benzodiazepines (associated with risks for tolerance and withdrawal), buspirone (generally less effective; causes minimal side effects); gabapentin (has mild anxiolytic properties), hydroxyzine, and mirtazapine (may cause sedation and weight gain)

Treatment of OCD: SSRIs — higher doses and longer durations are typically required, compared with treatment of depression or GAD (both of which improve within 1 mo of initiation of treatment); 2 to 3 mo of maximum Food and Drug Administration-approved doses may be needed to see significant improvement of OCD symptoms; clomipramine — considered the gold standard for OCD treatment, due to its strong serotoninergic effects; may cause more side effects; CBT — exposure and response prevention is highly effective; psychosurgery — consider for refractory OCD

Readings

del Casale A, Pomes LM, Bonanni L, et al. Pharmacogenomics-guided pharmacotherapy in patients with major depressive disorder or bipolar disorder affected by treatment-resistant depressive episodes: a long-term follow-up study. J Pers Med. 2022;12(2):316. doi:10.3390/jpm12020316; Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73(1):56-63. doi:10.1001/jamapsychiatry.2015.2235. Erratum in: JAMA Psychiatry. 2016;73(1):90; Newby JM, Hobbs MJ, Mahoney AEJ, et al. DSM-5 illness anxiety disorder and somatic symptom disorder: comorbidity, correlates, and overlap with DSM-IV hypochondriasis. J Psychosom Res. 2017;101:31-37. doi:10.1016/j.jpsychores.2017.07.010; Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T3 augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1519-30;quiz 1665. doi:10.1176/ajp.2006.163.9.1519; Pittenger C. The pharmacological treatment of obsessive-compulsive disorder. Psychiatr Clin North Am. 2023;46(1):107-119. doi:10.1016/j.psc.2022.11.005; QuickStats: percentage of adults aged ≥20 years who used antidepressant medications* in the past 30 days, by sex and marital status - National Health and Nutrition Examination Survey, United States, 2015-2018. MMWR Morb Mortal Wkly Rep. 2020;69(42):1555. doi:10.15585/mmwr.mm6942a8; Rush AJ, Fava M, Wisniewski SR, et al. Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Control Clin Trials. 2004;25(1):119-42. doi:10.1016/s0197-2456(03)00112-0; Schneider LS, Nelson JC, Clary CM, et al. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry. 2003;160(7):1277-85. doi:10.1176/appi.ajp.160.7.1277; Sonawalla SB, Rosenbaum JF. Placebo response in depression. Dialogues Clin Neurosci. 2002;4(1):105-13. doi:10.31887/DCNS.2002.4.1/ssonawalla.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Li was recorded at 57th Annual Recent Advances in Neurology, held February 14-16, 2024, in San Francisco, CA, and presented by the University of California, San Francisco School of Medicine. For information on upcoming CME activities from this presenter, please visit https://cme.ucsf.edu. Audio Digest thanks the speakers and University of California for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

NE151401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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