Depresion, mental status testing, addiction and skin and bone infectrions

1. Depresion, mental status testing, addiction and skin and bone infectrions 10/07/11

2. Which of the following is the most common comorbidity associated with nonresponse to antidepressants? A) Diabetes B) Posttraumatic stress disorder (PTSD) C) Hypothyroidism D) Substance abuse

3. Answer •  D) Substance abuse

4. Understanding antidepressant nonresponse • since physicians diagnose depression on basis of symptoms and history, many patients with other illnesses meet diagnostic criteria • (must rule out, eg, thyroid disease, unrecognized diabetes, malignancies) • medication selection—important • since predicting responses not possible, iterative trials required • adherence—one-third of patients choose not to refill prescriptions • in Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, each treatment failure resulted in loss of 10% to 20% of patients

5. According to data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, two-thirds of patients who responded to their treatments reported benefits after: A) 12 wk B) 8 wk C) 6 wk D) 3 wk

6. Answer •  C) 6 wk

7. Focus on improved methods of engaging, preparing, and ensuring follow-through with patients requiring continued treatment;duration—guidelines recommend 8-wk trial, but speaker argues that likelihood of response low if not seen after first 2 wk • disability, complexity, and comorbidities—patients with poor natural history or prognosis often have poor responses (10%-20% efficacy in some groups) and may require different framework of expectations or time course • focus on establishing unit of symptom benefit (not remission

8. Common causes of nonresponse • Nonadherence • Unrecognized bipolarity—antidepressants show poor efficacy in patients with bipolar disorder (BD) or bipolar spectrum features • unrecognized psychosis — late-life depression may present with delusions and hallucinations • psychotic depression often accompanies severe recurrent illness in patients 60 to 70 yr of age, but may occur earlier in life • psychosis plus depression in younger patients may indicate bipolarity • since patients may • mask delusions or hallucinations, watch for near-psychotic signs (eg, perplexity, slippage, blocking, nonsequiters, confusing logic or reasoning) • dosages of antipsychotics used to augment antidepressants do not adequately treat psychosis • unrecognized comorbidities—in studies, 5% to 10% of patients presenting with apparently uncomplicated depression found to have 1 significant systemic medical illness capable of affecting diagnosis or treatment outcomes • substance abuse most common comorbidity responsible for antidepressant failures (often masked) • reassess for abuse at every stage of treatment

9. Adequate treatment trials • 4- to 6-wk trials at full or maximum therapeutic dosage recommended • however, may discontinue in patients with significant side effects and no benefits at minimum dose • always document rationale for early discontinuation • speaker attempts trials with nutriceuticals, increased emphasis on psychotherapy, or transcranial magnetic stimulation in patients with history of intolerance to many (6-8) antidepressants • patients with extremely poor tolerability to one medication typically have similar responses to all agents in same class; • remission vs response — although remission may be ideal, patients showing significant improvement should continue current treatment • attempt augmentation strategies to induce remission in patients with partial response • STAR*D data — two-thirds of responsive patients showed results by 6 wk • speaker discourages 12-wk trails (without steady trend of improvement with acceptable tolerability

10. In STAR*D, patients who failed one adequate trial of an antidepressant showed: A) Superior response rates when switched to a multiple-action agent (eg, buproprion, venlafaxine) B) Superior response rates when switched to a second selective serotonin reuptake inhibitor (SSRI) C) Comparable response rates when switched to either multiple-action medications or SSRIs

11. Answer • C) Comparable response rates when switched to either multiple-action medications or SSRIs

12. Strategies for stage I resistance • switch within same class • switch across classes • adjunctive strategies • combining selected antidepressants • switching vs augmentation • Switching may be preferable (prevents costs of second treatment and allows targeted remediation of side effects

13. STAR*D data on medication switch outcomes • no statistically significant differences found among patient groups switched from citalopram to sertraline, bupropion, or venlafaxine • authors found same-class switching viable option (nearly as effective as switch to multiple-action agents) • nortriptyline and mirtazapine showed comparable efficacy • however, mirtazapine shows superior safety profile and tolerability (no cardiography or blood tests required for patients >40 yr of age

14. Benefits of augmentation strategies • response more rapid • No washout period needed • easier implementation (eg, no issues with cross-titration

15. Lithium has superior benefits as an augmentative agent when used with: A) Tricyclic antidepressants  B) SSRIs C) Serotonin and norepinephrine reuptake inhibitors D) Anxiolytics

16. Answer •  A) Tricyclic antidepressants 

17. Best evidence-supported adjunctive therapies • lithium — long history of use in enhancement of tricyclic antidepressants (TCAs) • requires blood level monitoring • significant side ef fects • less effective with modern antidepressants • has proven therapeutic efficacy • typically effective at 600 mg to 1200 mg daily (high blood levels not required) • thyroid augmentation — T3 hormone preferred (25-50 µg daily), since T4 not used for brain activity • showed comparable efficacy to lithium augmentation in STAR*D, but with easier implementation • One study linked efficacy to genetic polymorphisms affecting conversion of T4 to T3 • (possible explanation for inconsistent results); • buspirone — nonhabit-forming anxiolytic (via partial agonism of serotonin receptor 1A) • appears to enhance or modify effects of selective serotonin reuptake inhibitors (SSRI) • potentially difficult to use (due to wide dosage range [5 mg bid to 20 mg tid] and side effect burden); relieves anxiety and reverses sexual side effects when used with SSRI

18.  _______ is recommended for use in thyroid augmentation of depression treatments, due to its activity in the brain. A) Monoiodothyronine B) Diiodothyronine C) T3 hormone  D) T4 hormone

19. Answer •  C) T3 hormone 

20. According to STAR*D, augmentation of an antidepressant with _______ has superior benefits in patients with more severe anxiety. A) Buspirone B) Bupropion C) Lithium D) Lamotrigine

21. Answer •  B) Bupropion

22. Antidepressant combinations • many agents have complementary effects • no washout required • efficacy remains understudied • citalopram augmented by bupropion vs buspirone (STAR*D) • combinations showed comparable efficacy • bupropion showed superiority in patients with greater anxiety and buspirone showed superiority in patients with milder anxiety

23. Other options • adjunctive benzodiazepines —show benefits only with continuous use (ie, palliative but not curative) • use caution when initiating for chronic complicating anxiety due to high risk for long-term dependency • monoamine oxidase inhibitors (MAOIs) —classically effective agents with unique mechanisms of action • particularly effective in early-onset chronic depression with reversed vegetative features • in STAR*D level 4, many physicians failed to prescribe adequate dosages of MAOIs • mirtazapine plus venlafaxine found more effective than tranylcypromine (possibly due to relative ease of use • DR Stahl calls it California rocket full

24. Responses to sequential treatment in STAR*D • after 4 failed medication trials, only 10% of patients eventually achieve remission • increasing treatment resistance also increases risk for relapse after response (close follow-up and monitoring required

25. Atypical antipsychotics show proven efficacy in _______ of patients with depression. A) 55% B) 35% C) 20% D) 10%

26. Answer •  C) 20%

27. Augmentation with atypical antipsychotics (AAP) • Proven effective (compared to placebo), but only in 20% of patients and in trials of 6 to 8 wk • guidelines for use undetermined • long-term use gradually increases risk for metabolic side effects and tardive dyskinesia (in 1 yr follow-up of patients using adjunctive aripiprazole, several cases of reversible acute onset dyskinesia occurred [<1% of patients]) • Approved combinations — olanzapine plus fluoxetine • aripiprazole plus many antidepressants • quetiapine plus many antidepressants • risks —studies found olanzapine plus fluoxetine increased weight by average of 5.5 kg over 8 wk • speaker’s conclusions — use only when justified by severity or urgency • keep baseline of weight and metabolic activity • record abnormal involuntary movement scores in patients undergoing long-term treatmen

28. Augmentation with other mood stabilizers • lamotrigine most widely used • shows “quelching” effect in patients with history of posttraumatic stress disorder (PTSD) • covers subtle bipolar syndromes • speaker prefers AAPs due to superior clinical evidence

29. Modafinil and armodafinil augmentation • reduce symptoms of drowsiness and fatigue, but do not improve mood, optimism, or hedonic capacity • costly and often not covered by insurance • recommended only in patients reporting persistent difficulties with sleepiness, hypersomnolence, and fatigue

30. Dopaminergic options • pramipexole — nonhabit-forming selective dopamine agonist • shows antidepressant effects in small studies of treatment-resistant depression and BD • may cause drowsiness, lightheadedness, and inappropriate alertness at night (20% of patients discontinue

31. Conclusions • outcome measuring, following adherence, working through sequential treatment hierarchies, retrials, and confident use of TCAs, MAOIs, and electroconvulsive therapy • (and appropriate combinations of therapies), • depression can be successfully resolved within 1 yr in 90% of patients

32. _______ is shown to be the most accurate psychologic screening tool, but it requires more time than competing forms of testing. A) Mini-Mental State Examination B) Mini-Cog Assessment C) St. Louis University Mental Status Examination D) Montreal Cognitive Assessment

33. Answer • D) Montreal Cognitive Assessment

34. NT vs Mini-Mental State Examination (MMSE) • does not replace thorough cognitive assessment • outdated; has high falsepositive rate in patients >60 yr of age; fails to account for baseline performance in patients with above- or below-average level of education

35. Mini-Cog Assessment • recommended for assessing dementia • requires only 2 to 3 min • public domain • patients required to retain memory of 3 words while drawing picture of clock set to specific time • can be performed by any caregiver

36. Alternatives to MMSE • St. Louis University Mental Status • Examination— public domain • more difficult than MMSE • has higher expectations for healthy aging of brain • Brevity similar to that of MMSE, but yields far more accurate results • Montreal Cognitive Assessment—most accurate cognitive screening tool, but has slightly longer administration time • public domain • translated into >20 languages • easily score

37. Serial evaluation with NT should ideally be spaced _______ apart. A) 6 to 12 wk B) 3 to 6 mo C) 9 to 12 mo D) 1 to 2 yr

38. Answer • C) 9 to 12 mo

39. Nearly all forms of pleasure are associated with dopamine release in the: A) Nucleus accumbens B) Anterior insula C) Cingulate gyrus D) Brainstem

40. Answer • A) Nucleus accumbens

41. Disulfram causes a toxic reaction to alcohol by inhibiting the metabolism of: A) Ethyl glucuronide B) Acetaldehyde C) Acetic acid D) Phosphatidyl ethanol

42. Answer •  B) Acetaldehyde

43. _______ is most effective in patients with a strong family history of alcoholism and an early age of onset. A) Disulfram B) Naltrexone C) Acamprosate D) Baclofen

44. Answer • B) Naltrexone

45. _______ has been shown to prolong the time until relapse in patients with stimulant dependence. A) Bupropion B) Topiramate C) Modafinil D) Naltrexone

46. Answer • A) Bupropion

47. Background on addiction • brain disease characterized by compulsive behavior, continued substance use despite consequences, and persistent changes in brain structure and functioning • pathophysiology — all commonly abused substances act at synaptic level • synaptic effects cause cascade of intracellular changes that affect long-term reactivity, gene expression, and connectivity to other neurons • reward pathways — nearly all forms of pleasure coincide with dopamine release in nucleus accumbens (NAcc), serotonin release in brainstem, and activation of opioid receptors by endogenous opiate peptides in NAc

48. Management of alcohol dependence • Disulfiram: patients typically discontinue usage before relapsing; causes toxic reaction to alcohol by inhibiting metabolism of acetaldehyde (secondary stage of ethanol metabolism) • patient sensitivity varies (some report side effects when ingesting vinegar) • potential for severe hepatotoxicity (monitoring of liver function tests [LFTs] required) • has no effect on alcohol cravings • recommended for patients with high motivation to maintain sobriety, awareness of upcoming triggers, and supportive individuals who can witness patient's self-administratio

49. Naltrexone • blocks rewarding effects of alcohol at opioid receptors • dosing —50 to 100 mg daily; LFTs required • Poor compliance causes poor outcomes • depot preparation— monthly intramuscular injection slowly releases naltrexone into bloodstream at fixed rate • circumvents compliance issues efficacy— limited reduction in cravings • blunts response to alcohol if relapse occurs • most effective in patients with strong family history and early onset of alcoholism (possibly due to transcription variations in µ-opioid receptors) • blockading opioid receptors on GABA neurons inhibits dopamine release in NAc

50. Acamprosate • chemically similar to GABA • reduces glutamate transmission; mechanism of action— since alcohol acts as • substitute for GABA, endogenous production of GABA decreases with repeated intoxication • suppressed GABA results in compensatory increase of glutamate (causing anxiety, tremors, and potential seizures if patient withdraws from alcohol) • acamprosate helps restore GABA-glutamate balance • characteristics — few side effects; reduces cravings; may cause gastrointestinal irritation (rarely affects adherence) • requires large dose taken 3 times daily • Excreted through kidneys; efficacy—speaker reports lackluster results in United States (possibly due to different phenotypes of alcoholism