A34 Management of Depression, Bipolar Disorders, Obsessive-Compulsive Disorder, Chronic Schizophrenia and other Psychia

1. Jay S. Luxenberg, M.D. Clinical Professor, University of California, San Francisco Medical Director, Jewish Home, San Francisco A34 �Management of Depression, Bipolar Disorders, Obsessive-Compulsive Disorder, Chronic Schizophrenia and other Psychiatric Diagnoses in the Non-demented Residents of Long Term Care

2. Faculty Disclosures: Dr. Luxenberg has disclosed that he has no relevant financial relationship(s).

3. Learning Objectives: By the end of the session, participants will be able to: Conceptualize psychiatric illness in relationship to evolution of brain function Individualize and articulate treatment goals Use quantitative goals to titrate therapy to maximize goal achievement including remission when possible Recognize situations when psychiatric consultation needed

4. Non-Dementia Mental Health Illnesses in the Nursing Home � 560,000 U.S. nursing home residents had mental health illness other than dementia in 2002. This number exceeds the number hospitalized in psychiatric hospitals that year (51,000) Mental illness is a frequent contributing factor to nursing home placement

5. Proportions of persons newly admitted to nursing homes with dementia, mental illness, or both, 1999�2005

6. Proportions of persons admitted long-stay residents to nursing home with dementia, mental illness, or both, 1999�2004

7. Non-Dementia Mental Health Illnesses in the Nursing Home

8. Evolutionary Medicine: Psychiatry Emotions are adaptive responses that arise from mechanisms shaped by selection Emotions are modes of functioning, shaped by natural selection, that coordinate physiological, cognitive, motivational, behavioral, and subjective responses in patterns that increase the ability to meet the adaptive challenges of situations that have recurred over evolutionary time They are adaptations that are useful only in certain situations (Underwood, 1954). Like pain and sweating, they remain latent until an evolved mechanism detects cues associated with the situation in which they are advantageous. Unlike simpler adaptations, however, emotions are not unimodal responses to specific situations, like sweating in response to overheating. Instead, emotions adjust multiple component processes to create an organized response to the adaptive challenges of a given situation. For instance, appraisals that indicate a nearby predator arouse an emergency response that adjusts and coordinates many aspects of physiology and behavior. Physiology may influence cognition, and cognition may influence feeling, which may influence behavior and physiology in a complex, recursive sequence. Emotions are often elicited in situations where they are useless. This is an inevitable and adaptive outcome. Consider a signal detection analysis of the costs and benefits of panic in a particular situation. If the cost of a false alarm is low, for instance, 200 kcal and 10 minutes, and the cost of not experiencing panic in the presence of a real danger is high, say, 200,000 kcal of damage on average, then a normal system will express many false alarms. In this hypothetical case, the optimal system will express a panic attack whenever a cue indicates a greater than 1 in 1,000 chance that a predator is present. So, 999 out of 1,000 responses will be false alarms that are perfectly normal and useful in the long run. This �smoke detector principle� is crucial for understanding apparently unnecessary anxiety and depression (Nesse, 2005).They are adaptations that are useful only in certain situations (Underwood, 1954). Like pain and sweating, they remain latent until an evolved mechanism detects cues associated with the situation in which they are advantageous. Unlike simpler adaptations, however, emotions are not unimodal responses to specific situations, like sweating in response to overheating. Instead, emotions adjust multiple component processes to create an organized response to the adaptive challenges of a given situation. For instance, appraisals that indicate a nearby predator arouse an emergency response that adjusts and coordinates many aspects of physiology and behavior. Physiology may influence cognition, and cognition may influence feeling, which may influence behavior and physiology in a complex, recursive sequence. Emotions are often elicited in situations where they are useless. This is an inevitable and adaptive outcome. Consider a signal detection analysis of the costs and benefits of panic in a particular situation. If the cost of a false alarm is low, for instance, 200 kcal and 10 minutes, and the cost of not experiencing panic in the presence of a real danger is high, say, 200,000 kcal of damage on average, then a normal system will express many false alarms. In this hypothetical case, the optimal system will express a panic attack whenever a cue indicates a greater than 1 in 1,000 chance that a predator is present. So, 999 out of 1,000 responses will be false alarms that are perfectly normal and useful in the long run. This �smoke detector principle� is crucial for understanding apparently unnecessary anxiety and depression (Nesse, 2005).

9. Evolutionary Medicine: Psychiatry It�s helpful to think of emotions as a response � similar to pain, fever, sweating Just as pain and fever are useful responses to particular stimuli like infections but can cause problems as �false positives� or require management when no longer useful, emotions can be problematic when they are not helpful or their benefit is outweighed by harm. They are adaptations that are useful only in certain situations (Underwood, 1954). Like pain and sweating, they remain latent until an evolved mechanism detects cues associated with the situation in which they are advantageous. Unlike simpler adaptations, however, emotions are not unimodal responses to specific situations, like sweating in response to overheating. Instead, emotions adjust multiple component processes to create an organized response to the adaptive challenges of a given situation. For instance, appraisals that indicate a nearby predator arouse an emergency response that adjusts and coordinates many aspects of physiology and behavior. Physiology may influence cognition, and cognition may influence feeling, which may influence behavior and physiology in a complex, recursive sequence. Emotions are often elicited in situations where they are useless. This is an inevitable and adaptive outcome. Consider a signal detection analysis of the costs and benefits of panic in a particular situation. If the cost of a false alarm is low, for instance, 200 kcal and 10 minutes, and the cost of not experiencing panic in the presence of a real danger is high, say, 200,000 kcal of damage on average, then a normal system will express many false alarms. In this hypothetical case, the optimal system will express a panic attack whenever a cue indicates a greater than 1 in 1,000 chance that a predator is present. So, 999 out of 1,000 responses will be false alarms that are perfectly normal and useful in the long run. This �smoke detector principle� is crucial for understanding apparently unnecessary anxiety and depression (Nesse, 2005).They are adaptations that are useful only in certain situations (Underwood, 1954). Like pain and sweating, they remain latent until an evolved mechanism detects cues associated with the situation in which they are advantageous. Unlike simpler adaptations, however, emotions are not unimodal responses to specific situations, like sweating in response to overheating. Instead, emotions adjust multiple component processes to create an organized response to the adaptive challenges of a given situation. For instance, appraisals that indicate a nearby predator arouse an emergency response that adjusts and coordinates many aspects of physiology and behavior. Physiology may influence cognition, and cognition may influence feeling, which may influence behavior and physiology in a complex, recursive sequence. Emotions are often elicited in situations where they are useless. This is an inevitable and adaptive outcome. Consider a signal detection analysis of the costs and benefits of panic in a particular situation. If the cost of a false alarm is low, for instance, 200 kcal and 10 minutes, and the cost of not experiencing panic in the presence of a real danger is high, say, 200,000 kcal of damage on average, then a normal system will express many false alarms. In this hypothetical case, the optimal system will express a panic attack whenever a cue indicates a greater than 1 in 1,000 chance that a predator is present. So, 999 out of 1,000 responses will be false alarms that are perfectly normal and useful in the long run. This �smoke detector principle� is crucial for understanding apparently unnecessary anxiety and depression (Nesse, 2005).

10. A Useful Framework Think of the propensity to have an emotion as a valuable trait � e.g. having some anxiety when confronted with potential danger is going to make it more likely to survive to pass on your genes. Multiple genes would be involved in the evolution of this propensity. Many alleles could relate to anxiety disorders.

11. Psychiatric Illnesses and Aging Illnesses of Childhood onset Attention deficit/hyperactivity Gilles de la Tourette syndrome Obsessive�compulsive disorder Illnesses of Adolescence onset Schizophrenia Illnesses of Adult onset

12. Depression & Anxiety Tremendous overlap � � 85% of patients with depression have significant anxiety; � 90% of Generalized Anxiety Disorder (GAD) patients have history of major depression or significant depressive symptoms Both conditions women 2x > men Depression � relapsing & remitting; Anxiety � chronic New information on biological links between the two conditions

13. Biology of Depression & Anxiety Are Linked: Caspi et al: life stress, s/l polymorphism of serotonin transporter and depression - Science 18 July 2003; 301: 386-38 Zhang et al: TPH polymorphism and unipolar depression - Neuron 2005;45:11-6 Hariri et al: s/l polymorphism of serotonin transporter and amygdala response to fear Arch Gen Psychiat 2005 62:146-52 Kim et al: Monoamine transporter gene polymorphisms and antidepressant response JAMA 2006;296:1609-1618

14. Let�s Think of Depression & Anxiety in a New Way Why can some people survive horribly stressful life events without clinically evident depression or anxiety?

15. Let�s Think of Depression & Anxiety in a New Way A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele.

16. Let�s Think of Depression & Anxiety in a New Way

18. Let�s Think of Depression & Anxiety in a New Way Recent studies have identified an autosomal dominant gene that may account for � 10% of unipolar depression patients, is strongly linked to suicidality, and may predict poor response to SSRI

19. Let�s Think of Depression in a New Way 10% (9) of 87 elderly patients with a history of major depression had a mutated gene variant of the gene for tryptophan hydroxylase-2 (Tph2) that produces 80% less serotonin Among 219 controls, three subjects carried this mutation. These three control subjects still had problems, including generalized anxiety, mild depression and family history of alcohol abuse Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 200410.1016/..2004.12.014/S0896627304008086 Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 200410.1016/..2004.12.014/S0896627304008086

20. Summary of Subjects Carrying Functional (G1463A) SNP in hTPH2 All patients listed above were Caucasians, except subject 1541, who was African American. All patients listed above were Caucasians, except subject 1541, who was African American.

21. Let�s Think of Depression in a New Way This gene seems specific for unipolar depression: No one in a group of 60 patients with bipolar depression had this gene variant. Seven of the 9 depressed subjects with this gene variant failed to respond to SSRIs The other two required high doses Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 200410.1016/..2004.12.014/S0896627304008086 Campos SB, Miranda DM, Souza BR et al. Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior. J Psychiatr Res. 2009 Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 200410.1016/..2004.12.014/S0896627304008086 Campos SB, Miranda DM, Souza BR et al. Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior. J Psychiatr Res. 2009

22. Let�s Think of Depression in a New Way This same gene is related to risk-taking behaviors, unrelated to the presence of depression. Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 200410.1016/..2004.12.014/S0896627304008086 Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 200410.1016/..2004.12.014/S0896627304008086

23. Let�s Think of Anxiety in a New Way Individuals carrying the less efficient s allele of the 5-HTT gene promoter exhibit an increased amygdala response to fearful stimuli compared with those homozygous for the l allele

24. Amygdala Response s group > 1 group

25. Amygdala Response In more recent studies, high risk allele carriers (S or L(G)) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with depression and life-time psychiatric hospitalization as an index of chronicity. 5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression. Dannlowski U et. al. Neuropsychopharmacology. 2007 Apr 4 This response is blunted by SRIs Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Harmer CJ et. al. Biol Psychiatry. 2006 May 1;59(9):816-20

26. In Korean Adults with MDD Particular common allelic variations of serotonin and norepinephrine reuptake genes were associated with response to SSRIs and nortriptyline, respectively 5-HTT promoter region s/l variant �s� associated with poor SSRI response in �white� patients was associated with the opposite � good SSRI response in Koreans. It was also associated with better nortriptyline response. Certain combinations of 2 polymorphisms were even more strongly associated with treatment response Kim et al: Monoamine transporter gene polymorphisms and antidepressant response JAMA 2006;296:1609-1618 patients were mostly elderly (77% age 50 years), and most (60%) had late-onset illnesses with few previous depressive episodes. There were no major differences by sex, number of episodes, age at onset, or HAM-D scores before or after treatment between the NRI-treated and SSRI-treated groups (TABLE 1). Patients treated with SSRIs were older (mean [SD] age, 59.9 [12.6] years) than those treated with nortriptyline (mean [SD] age, 55.8 [12.4] years). The mean age at onset of major depressive disorder was in the early to mid-50s (Table 1). Rate of response to antidepressants was 124 (60%) of 208 patients who completed the 6-week treatment trial; 55 (62%) of 89 patients who received the NRI and 69 (58%) of 119 patients who received an SSRI (P=.58). Rate of remission did not differ by drug class (26 [29%] of 89 in NRI group vs 34 [29%] of 119 in SSRI group). The overall distribution of response, remission, and nonresponse did not differ by drug class (P=.84). As to the prediction of differential drug response, our preliminary data analysis suggests that patients carrying the GG polymorphism of NET G1287A will have a statistically significantly superior rate of response to NRI treatment than to SSRI treatment (83.3% vs 58.7% [P=.006]; OR, 3.52 [95% CI, 1.39-8.95]). As this genetic subgroup comprised 56% of the population (117/208 cases), this result may prove to have salience for clinical practice. This preliminary finding needs to be tested in studies specifically designed to examine differential response to drug class by genotype.patients were mostly elderly (77% age 50 years), and most (60%) had late-onset illnesses with few previous depressive episodes. There were no major differences by sex, number of episodes, age at onset, or HAM-D scores before or after treatment between the NRI-treated and SSRI-treated groups (TABLE 1). Patients treated with SSRIs were older (mean [SD] age, 59.9 [12.6] years) than those treated with nortriptyline (mean [SD] age, 55.8 [12.4] years). The mean age at onset of major depressive disorder was in the early to mid-50s (Table 1). Rate of response to antidepressants was 124 (60%) of 208 patients who completed the 6-week treatment trial; 55 (62%) of 89 patients who received the NRI and 69 (58%) of 119 patients who received an SSRI (P=.58). Rate of remission did not differ by drug class (26 [29%] of 89 in NRI group vs 34 [29%] of 119 in SSRI group). The overall distribution of response, remission, and nonresponse did not differ by drug class (P=.84). As to the prediction of differential drug response, our preliminary data analysis suggests that patients carrying the GG polymorphism of NET G1287A will have a statistically significantly superior rate of response to NRI treatment than to SSRI treatment (83.3% vs 58.7% [P=.006]; OR, 3.52 [95% CI, 1.39-8.95]). As this genetic subgroup comprised 56% of the population (117/208 cases), this result may prove to have salience for clinical practice. This preliminary finding needs to be tested in studies specifically designed to examine differential response to drug class by genotype.

27. Interaction with Dementias No evidence the genes so far identified with depression and anxiety are involved with etiology (or incidence) of any dementing illness If you do develop dementia, they are associated with development of behavioral and psychological symptoms Role of Serotonin Transporter Polymorphisms in the Behavioural and Psychological Symptoms in Probable Alzheimer Disease Patients. - Pritchard et al., 2007, Dement Geriatr Cogn Disord, 24, 201-206 Role of 5HT(2A) and 5HT(2C) polymorphisms in behavioural and psychological symptoms of Alzheimer's disease. Pritchard et al., 2006, Neurobiol Aging

28. Depression Up to 25% of nursing home residents Elderly are �12% of population but 25% of suicides - high rate of success

29. Factors Impacting Diagnosis of Depression The �normative fallacy��that is, the belief that symptoms of depression are �normal� or �expectable� given the patient�s age, social circumstances (including recent losses), and medical condition Attributing neurovegetative symptoms and signs (such as loss of energy, poor appetite, and disturbed sleep) to concomitant medical problems

30. Diagnosing Depression Interfering with diagnosis Sensory deficits Medical illnesses Cognitive deficits Cultural factors

31. Tough Differentials Somatoform disorders versus physical illness accompanied by depression Substance abuse causing depression versus depression causing substance abuse Progressive dementia causing reactive depression versus depression resulting in symptoms of dementia

32. Tough Differentials Anorexia in depression versus anorexia in malignancy, dementia or other medical illness Depression in late dementias versus withdrawal and silence as stage in progressive dementia

33. 5 Question Geriatric Depression Scale Are you basically satisfied with your life? Do you feel pretty worthless the way you are now? Do you often get bored? Do you often feel helpless? Do you prefer to stay at home rather than going out and doing new things? Positive answers for depression screening are yes to questions 2, 3, 4, and 5 and no to question 1 2 or higher indicates possible depression Hoyl MT - J Am Geriatr Soc - 1999 Jul; 47(7): 873-8

34. DSM IV Diagnostic Criteria of Major Depressive Episode 5 criteria must be present nearly every day for a minimum of 2 weeks and represent a change from previous functioning 1.)* Depressed mood (e.g. crying) 2.)* Loss of interest or pleasure * (One of these two must be present)

35. DSM IV Diagnostic Criteria of Major Depressive Episode 5/9 symptoms needed for diagnosis 3.) Significant weight loss or gain or change in appetite 4.) Insomnia or hypersomnia 5.) Psychomotor agitation or retardation 6.) Decreased energy or easy fatigability

36. DSM IV Diagnostic Criteria of Major Depressive Episode 5/9 symptoms needed for diagnosis 7.) Feelings of worthlessness or excessive or inappropriate guilt 8.) Decreased ability to think or concentrate, or indecisiveness 9.) Recurrent thoughts of death or suicide

37. DSM IV Diagnostic Criteria of Major Depressive Episode The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).

38. Bereavement versusMajor Depressive Episode In a major depressive episode after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

39. Grief Uncomplicated grief (bereavement) can include all the features of major depression except suicidality, psychosis, and sever loss of functionality Although time course of normal grief is variable, most patients should be at or moving toward baseline at one year. Depression is common after bereavement, and is valuable to identify/differentiate

40. Complicated Grief 10-20% of bereaved individuals

41. Depression Treatment Think of treating depression as analogous to treatment of hypertension � pick a measure (Hamilton Depression Scale, MADRAS, GDS, Cornell, etc) � measure it before treatment, and periodically during course of treatment.

42. Depression Treatment Most patients will respond to standard antidepressant therapy if given in adequate dose for adequate duration Some patients will benefit from insight oriented therapies or other counseling modalities Some patients will benefit from acute inpatient psychiatric hospitalization Treatment failures will require consultation - may benefit from augmentation strategies

44. Treatment Let�s digest the stream of information from the STAR*D studies published beginning in 2006 to allow our patients to benefit from a new paradigm for management of the depression/anxiety spectrum Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 20042005 Jan 6;45(1):11-6 Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 20042005 Jan 6;45(1):11-6

45. STAR*D Study Sequenced Treatment Alternatives to Relieve Depression (STAR*D) 35 million $ NIMH sponsored study @ 14 regional centers, each with 2-4 sites Generalizable population of outpatients 18�75 years of age with nonpsychotic major depressive disorder Treated initially with citalopram, a prototype of selective serotonin reuptake inhibitors (SSRIs)

46. STAR*D Study Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Measurement-based care includes the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual describing when and how to modify medication doses based on these measures.

47. Quick Inventory of Depressive Symptomatology (QIDS) 16 item, 27 point scale Clinician Administered (QIDS-C16) Self-Administered (QIDS-SR16) Available translated into 13 languages Easy to score - =5 is remission A QIDS-SR16 total score of 5 was comparable to a MADRS total score of 7 or 8 (7.5) http://www.ids-qids.org Carmody et al J Affect Disord. 2006 Oct;95(1-3):115-8. Carmody et al J Affect Disord. 2006 Oct;95(1-3):115-8.

48. Remission as the goal of Rx Remission, the virtual absence of symptoms, is the aim of depression treatment because it is associated with better function and a better prognosis than is response without remission. Response is typically defined as a clinically meaningful reduction in symptoms (e.g., a reduction of at least 50% in baseline symptom levels).

49. Remission as the goal of Rx Response that falls short of remission is suboptimal because it is associated with Continued disabling symptoms, Negative effects on other axis I and axis III disorders Higher rates of relapse and recurrence Poorer work productivity More impaired psychosocial functioning Higher levels of health care use Potentially higher risk for suicide.

50. Time to Relapse in MDD

51. STAR*D Study Initial Rx Sequenced Treatment Alternatives to Relieve Depression (STAR*D) The overall remission rate was 27.5% (N=790) with the HAM-D definition (primary outcome) and 32.9% (N=943) with the QIDS-SR definition. Remission rates were comparable in primary and psychiatric care - QIDS-SR (32.5% versus 33.1%) The overall QIDS-SR response rate was 47% (N=1,343) (46% primary care, 48% psychiatric care)

52. What If Initial Treatment Fails?

53. Sequenced Treatment Alternatives Sequenced Treatment Alternatives Include Maintain dose and extend treatment Dose escalation Augmentation/Combination therapy Switching Nonpharmacological therapy e.g. cognitive behavioral can be added or switched to if not in place initially

54. STAR*D QIDS-SR Exit Scores

55. STAR*D 2nd, 3rd Level Rxs 2nd � Switch to Bupropion-SR, Sertraline, , N Engl J Med 2006;354:1231-42 2nd � Augmentation with Bupropion-SR or Buspirone � Trivedi et al, N Engl J Med 2006;354:1243-52 3rd - Augmentation with Lithium or T3 � Nierenberg et al, Am J Psychiatry 2006; 163:1519�1530 or Venlafaxine-XR � Rush et al After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms (� 25% remission rates) after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. Augmentation of citalopram with either sustained-release bupropion or buspirone (� 30% remission rates) appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. Remission rates with lithium and T3 augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest (< 20% remission rates) and did not differ significantly. The lower side effect burden and ease of use of T3 augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms (� 25% remission rates) after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. Augmentation of citalopram with either sustained-release bupropion or buspirone (� 30% remission rates) appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. Remission rates with lithium and T3 augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest (< 20% remission rates) and did not differ significantly. The lower side effect burden and ease of use of T3 augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.

56. STAR*D 3rd, 4th Level Rxs 3rd - Mirtazapine and Nortriptyline Following two Failed Antidepressant Medication Trials for Depression � Fava et al, Am J Psychiatry 2006; 163:1161�1172 4th � Tranylcypromine Versus Venlafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression � McGrath et al, Am J Psychiatry 2006; 163:1531�1541 Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder. Conclusions: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments.Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder. Conclusions: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments.

57. STAR*D - Genetic Markers Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein - Perlis et al., 2007, Arch Gen Psychiatry, 64, 689-97 Association of GRIK4 [which codes for the kainic acid-type glutamate receptor KA1] with outcome of antidepressant treatment in the STAR*D cohort - Paddock et al., 2007, Am J Psychiatry, 164, 1181-8

58. Genetics of Antidepressant Response Several genes with polymorphisms were identified in STAR*D and subsequently also seen in other studies that correlate with remission achievement with antidepressant therapy

59. URLs STAR*D � instruments, publications, methodology, etc. http://www.edc.gsph.pitt.edu/stard/public/index.html QIDS � instruments, scoring, etc. http://www.ids-qids.org

60. Nonpharmacological Treatments for Depression in Nursing Home Residents

61. Nonpharmacological Treatments for Depression in Nursing Home Residents

62. Pharmacological Treatments for Depression in Nursing Home Residents

63. Pharmacological Treatments for Depression in Nursing Home Residents

64. Antidepressants Tricyclic Antidepressants Heterocyclics Serotonin Selective Reuptake Inhibitors Novel Antidepressants Monoamine Oxidase Inhibitors Electroconvulsive Therapy

65. Choice of Antidepressant Severity of depression Symptomatology e.g. withdrawal v. agitation, insomnia v. sedation, etc. Patient characteristics e.g. obesity v. malnutrition, coexistent medical illnesses Cost Social factors e.g. need for medication supervision Prior history of response

66. Norepinephrine Reuptake Inhibitors Nortriptyline Desipramine �SNRIs� e.g. reboxetine � none yet available in US

67. Nonspecific Reuptake Inhibitors Trazodone Amitriptyline Doxepin

68. Selective Serotonin Reuptake Inhibitors Fluoxetine Paroxetine Sertraline Citalopram Escitalopram

69. �Dual Action� Reuptake Inhibitors Venlafaxine Duloxetine

70. Selective Serotonin Reuptake Inhibitors Differentiating features: Pharmacokinetics - primarily excretion e.g. �half-life� of drug and metabolites Metabolizing enzyme induction (P-450 cytochrome isoenzymes IA2, IIC, IID6, IIIA4) Dosing convenience, availability of several dosage forms Additional activities e.g. receptor antagonism, other reuptake inhibition Cost

71. Drugs That May Cause Serotonin Syndrome with SSRIs Ecstasy Cocaine Lithium St John's wort (Hypericum) - herbal antidepressant Diethylpropion - an amphetamine Dextromethorphan - found in many cough suppressants BuSpar (buspirone) - for anxiety Eldepryl (selegiline) - for Parkinson's Disease Anti-epileptics - Tegretol, (carbamazepine) Analgesics - pethidine, Fortral (pentazocine), Tramal (tramadol), fentanyl Anti-migraine drugs - Naramig (naratriptan), Imigran (sumatriptan), Zomig (zolmitriptan) Appetite suppressants - phentermine and fenfluramine Tryptophan - an amino acid

72. Novel Antidepressants Bupropion Mirtazapine 5-HT1A Agonists 5-HTB Antagonists

73. Reversible Inhibitors Of Monoamine Oxidase Type A (RIMAs) Moclobemide Brofaromine Available in much of the world but not US Better tolerated but less effective than MAOIs

74. Monoamine Oxidase Inhibitors (MAOIs) Phenelzine (Nardil) Tranylcypromine (Parnate) May be more effective for atypical depression, and when primary complaints are boredom and apathy Dietary restrictions!

75. Electroconvulsive Therapy Can be safer than pharmacotherapy Faster onset of action than drugs Memory impairment can be minimized but not eliminated as a risk Modern techniques are better tolerated than previous techniques

76. Transcranial Magnetic Stimulation (TMS) A non-invasive technique that uses a powerful electro-magnet placed on the scalp to alter brain activity Repetitive TMS, using varying frequencies and intensities, can increase or decrease excitability in the cortical area directly targeted by the stimulation Until additional convincing evidence of its clinical efficacy and safety is available, TMS remains an experimental intervention

77. Methylphenidate Inadequate trials to define efficacy, but anecdotal benefit in alertness, fatigue and apathy symptoms when used short-term May provide early benefit while waiting for effect of other treatments Anorexia and insomnia are among risks, but studies suggest it is well tolerated

78. Depression Treatment Review Most patients will respond to standard antidepressant therapy if given in adequate dose for adequate duration Some patients will benefit from insight oriented therapies or other counseling modalities Some patients will benefit from acute inpatient psychiatric hospitalization Treatment failures will require consultation - may benefit from augmentation strategies

79. Anxiety Spectrum Illnesses Generalized Anxiety Disorder Obsessive Compulsive Disorder Panic Disorder Social Anxiety Disorder and other Phobic Disorders New onset of any of the anxiety spectrum illnesses is rare in old age

80. Anxiety Anxiety in the elderly occurs most commonly in a wide range of physical disorders and in mental disorders other than primary anxiety disorders Drugs can cause anxiety Anticholinergic drugs, antidepressants, �-agonists, caffeine, digoxin, OTC sympathomimetic drugs, theophylline, thyroid replacement

81. Primary Anxiety Disorders Primary anxiety disorders generalized anxiety disorder obsessive-compulsive disorder panic disorder phobic disorders stress disorder (e.g., acute stress disorder, posttraumatic stress disorder)

82. Obsessive�Compulsive Disorder OCD is the fourth most common mental disorder and is diagnosed nearly as often as asthma and diabetes mellitus Symptoms of OCD tend to abate with aging. It occurs about equally in men and women

83. Diagnosis of GAD - DSM-IV Excessive anxiety and worry for = 6 months At least 3 additional symptoms Restlessness Easily fatigued Difficulty concentrating Irritability Muscle tension Disturbed sleep Focus of worry not confined to features of other Axis I disorders According to the DSM-IV, the essential feature of generalized anxiety disorder (GAD) is excessive anxiety and worry, occurring more days than not for a period of at least 6 months. The anxiety and worry are accompanied by at least three additional symptoms such as restlessness, being easily fatigued, difficulty concentrating, irritability, muscle tension, and disturbed sleep. The anxiety and worry are difficult to control, and are not confined to features of other Axis I disorders, such as having a panic attack (panic disorder), or being embarrassed in public (social anxiety disorder). Individuals afflicted with GAD report subjective distress due to constant worry, and may experience impairment in social, occupational, or other important areas of functioning. Reference 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association; 2000.According to the DSM-IV, the essential feature of generalized anxiety disorder (GAD) is excessive anxiety and worry, occurring more days than not for a period of at least 6 months. The anxiety and worry are accompanied by at least three additional symptoms such as restlessness, being easily fatigued, difficulty concentrating, irritability, muscle tension, and disturbed sleep. The anxiety and worry are difficult to control, and are not confined to features of other Axis I disorders, such as having a panic attack (panic disorder), or being embarrassed in public (social anxiety disorder). Individuals afflicted with GAD report subjective distress due to constant worry, and may experience impairment in social, occupational, or other important areas of functioning. Reference 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association; 2000.

84. Despite the evolution of diagnostic criteria for GAD, epidemiologic studies using criteria from DSM-III, DSM-III-R, DSM-IV, and the Composite International Diagnostic Interview (CIDI) have found fairly consistent prevalence rates for GAD. Prevalence estimates for adults living in the community are between 1.5 percent and 3 percent for current GAD, 3 percent to 5 percent for GAD in the past year, and 4 percent to 7 percent for lifetime GAD. References 1. Blazer DG, Hughes D, George LK, et al. Generalized Anxiety Disorder. In: Robins LN, Regier DA, eds. Psychiatric Disorders in America. New York, NY: The Free Press; 1991:180-203. 2. Carter RM, Wittchen HU, Pfister H, et al. One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety. 2001;13:78-88. 3. Kessler RC, Dupont RL, Berglund P, et al. Impairments of twelve-month independent and comorbid generalized anxiety disorder and major depression in two national surveys. Am J Psychiatry. 1999;156:1915-1923. 3. Wittchen H-U, Zhao S, Kessler R, et al. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:355-364.Despite the evolution of diagnostic criteria for GAD, epidemiologic studies using criteria from DSM-III, DSM-III-R, DSM-IV, and the Composite International Diagnostic Interview (CIDI) have found fairly consistent prevalence rates for GAD. Prevalence estimates for adults living in the community are between 1.5 percent and 3 percent for current GAD, 3 percent to 5 percent for GAD in the past year, and 4 percent to 7 percent for lifetime GAD. References 1. Blazer DG, Hughes D, George LK, et al. Generalized Anxiety Disorder. In: Robins LN, Regier DA, eds. Psychiatric Disorders in America. New York, NY: The Free Press; 1991:180-203. 2. Carter RM, Wittchen HU, Pfister H, et al. One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety. 2001;13:78-88. 3. Kessler RC, Dupont RL, Berglund P, et al. Impairments of twelve-month independent and comorbid generalized anxiety disorder and major depression in two national surveys. Am J Psychiatry. 1999;156:1915-1923. 3. Wittchen H-U, Zhao S, Kessler R, et al. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:355-364.

85. Treating Anxiety to Remission Similar self-administered scales exist for anxiety, e.g. Zung self-rating Anxiety Scale Although no equivalent of STAR*D exists for anxiety treatment, measurement approach is equally useful Patience is a virtue as evidenced by Bielski 2005 study Carmody et al J Affect Disord. 2006 Oct;95(1-3):115-8. Carmody et al J Affect Disord. 2006 Oct;95(1-3):115-8.

86. Remission Rate in GAD

87. Obsessive Compulsive Disorder Obsessive compulsive disorder is not obsessive compulsive personality disorder A confusion of psychiatric terminology

88. OCD:� Anxiety Disorder Characterized By: Obsessions i.e. persistent, intrusive, inappropriate thoughts, images or impulses Compulsions i.e. repetitive acts to reduce the anxiety of the obsessions Person recognizes the symptoms as unreasonable Symptoms are distressful (�ego-dystonic�), time-consuming

89. Obsessive Compulsive Personality Disorder A long term, relatively stable patterns�of perceiving one�s self and environment characterized by: Traits such as orderliness and perfectionism at the expense of flexibility Attention to details, order, lists, and/or rules� Overconscientious and scrupulous� Reluctance to delegate� Rigidity and stubbornness

90. Obsessive Compulsive Disorder Patient safety Patients with OCD have higher potential for self-injury than general population� OCD can co-exist with other psychiatric disorders e.g. depression, bipolar������ disorder or other anxiety disorders.� OCD can be due to a medical disorder e.g. head trauma, ADR to medications

91. OCD Treatment Severity of symptoms tend to go down with age � �burns out� No controlled studies of OCD treatment in the elderly

92. OCD Treatment Options are medications, psychotherapy, or a combination of both Psychotherapy, specifically Cognitive Behavioral Therapy (CBT),� if� patient not����������������������� depressed or anxious and able to cooperate Medications when patient unable to cooperate with CBT, has had a past response to�medications, highly anxious or depressed������������������������ Combination when either treatment alone ineffective

93. OCD Treatment - Cognitive Behavioral Therapy (CBT) Requires specific training������������������������ Two variants: Exposure and response prevention���������������������������������������������� Cognitive interventions of identification, challenge, and�modification of faulty beliefs��������

94. OCD Treatment - Specific Meds Clomipramine (Anafranil) -� a mixed serotonin/norepinephrine reuptake blocker Highly effective Problematic ADR e.g. QTc prolongation Highly anticholinergic���������������������� Fluoxetine (Prozac), fluoxetine (Luvox), paroxetine (Paxil), sertraline (Zoloft)����������������������������������� Above are only FDA approved meds; citalopram (Celexa) has been studied�����������������������������������

95. OCD Treatment - Quantization Rating the severity of symptoms:����������������������� Number of hours per day patient is symptomatic����������������������� Record of actively avoided items or situations Yale-Brown Obsessive compulsive Scale (Y-BOCS) Obsessive-Compulsive Inventory

96. Panic A panic attack is the sudden onset of a discrete, brief period of intense discomfort or fear accompanied by somatic or cognitive symptoms. Panic disorder is occurrence of repeated panic attacks typically accompanied by fears about future attacks or changes in behavior to avoid situations that might predispose to attacks.

97. Panic Panic attacks in the elderly are rare. Symptoms of panic attacks in the elderly tend to be less severe. However, some elderly present with new-onset panic disorder manifesting as chest pain.

98. Panic Treatment Education Two forms of psychotherapy have proven effective: exposure therapy (confront fears) cognitive-behavioral therapy (recognize and control reaction to whatever triggers the panic and modify behavior so that it is more adaptive than simply avoiding the trigger)

99. Panic Treatment When panic attacks cause elderly patients to avoid certain places or situations, treatment is likely to require drug therapy in addition to psychotherapy. Antidepressants are often used. SSRIs and SNRIs based on side-effects and FDA approvals Intermediate-acting can be used if other therapies are ineffective.

100. Phobic Disorders Phobic disorders consist of persistent, unreasonable, intense fears (phobias) of situations, circumstances, or objects. The fears provoke anxiety and avoidance. Social phobia may be especially disabling in the elderly, particularly when an elderly person has developed the phobia secondary to an embarrassing experience in public (such as falling or incontinence)

101. Bipolar Disease in the Elderly Becomes less common with age Accounts for 8-10% of late life psychiatric admissions Is associated with neurologic factors in late-onset groups A heterogeneous life-long illness

102. Bipolar Disease in the Elderly So far, etiology is not related to the same genes identified in unipolar depression or anxiety

103. Bipolar Disease in the Elderly Very little of the heterogeneity of clinical presentation of bipolar disease is related to age of onset

104. Bipolar Disease in the Elderly Clinically important to identify � risk of mania if treating depression without mood stabilizer, higher with short 5-HTTLPR Mania may be misidentified as delirium Dearth of treatment trials in elderly

105. Bipolar Disease in the Elderly Depression in bipolar disease may be less responsive to antidepressant therapy, and it is controversial whether initial antidepressant therapy and/or maintenance is always appropriate

106. Mood Stabilization Lithium remains the �gold standard� with greatest efficacy and database. In general populations, mood stabilizer use frequency is valproate > lithium > carbamazepine or oxcarbazepine > lamotrigine There are few studies on the elderly, none specifically in SNFs

107. Management of Mania Consider psychiatric consultation/psychiatric hospitalization Pharmacologic management is usually combination of mood stabilizer and antipsychotic medication SNF risks include self injury, falls. Irritability can lead to resident-to-resident violence. Grandiosity can lead to financial misadventures.

108. Where Are We Going? Depression and anxiety syndromes will likely be influenced by many different genes and acquired states such as stroke and Parkinson�s disease Subgroups will be defined that predict response and side effects, allowing drug treatment to be tailored to improve odds of successful treatment

109. Meanwhile! Aggressive measures to recognize and treat psychiatric illness �screening, MDS, etc. Use of scales to monitor treatment efficacy � think of anxiety and depression like we think of hypertension, diabetes or high cholesterol Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 20042005 Jan 6;45(1):11-6 Report: Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major DepressionXiaodong Zhang, Raul R. Gainetdinov, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Lauranell H. Burch, Redford B. Williams, David A. Schwartz, K. Ranga R. Krishnan, and Marc G. CaronNeuron. Published online Dec. 9, 20042005 Jan 6;45(1):11-6

110. Treatment Considerations Emphasis on pharmacotherapy is in part an artifact of reimbursement mechanisms and availability of nonpharmacological therapy (such as Cognitive-Behavioral Therapy), which is effective on its own and as an adjunct Selective Serotonin Reuptake Inhibitors (SSRIs) are efficacious for both depression and anxiety, and help prevent relapse of both Although FDA approved indications differ amongst agents and formulations of agents, the biggest differences are in tolerability and side-effect profile Possible drug-drug interactions, weight gain, and sexual side-effects should be considered when choosing an agent

111. Treatment Considerations Dual action SRIs and NRIs do not have quicker onset of action and are not more likely to achieve remission than SRIs Quantitative monitoring with a scale facilitates titration, and achievement of remission Consider electroconvulsive therapy or acute psychiatric hospitalization when normal measures fail or patient particularly fragile

112. Treatment Considerationsfor Anxiety SRIs are first line pharmacotherapy - benzodiazepines should be reserved for short-term, breakthrough and second-line therapy Patience is often rewarded - note remission rate increases over months (see Bielski reference) Generalized anxiety disorder is a life-long condition, and relapse rates off treatment are high

113. Psychosis Per DSM IV-TR, the narrowest definition of psychosis requires hallucinations and delusions with loss of insight. Delusions are false, fixed, idiosyncratic beliefs that are maintained despite evidence to the contrary. Hallucinations are abnormal perceptions without a physical stimulus that can involve any sensory modality However, broader definitions of psychosis are allowed for DSM IV-TR defined diagnoses, such as brief psychotic disorder, which may require only disorganized speech or behavior. ForHowever, broader definitions of psychosis are allowed for DSM IV-TR defined diagnoses, such as brief psychotic disorder, which may require only disorganized speech or behavior. For

114. Hallucinations

115. Hallucinoses Somatic hallucinoses (Charles Bonnet syndrome and musical hallucinosis) are syndromes associated with sensory deficits. The most important reason to recognize them is to differentiate them from true psychoses, to avoid inappropriately use of medication. They often occur in the setting of very mild or early dementia

116. Schizophrenia in the SNF Schizophrenic Disorders Mood-incongruent Paranoid States 2 general categories: onset earlier in life, now aged, and new onset. New onset then divided into 1.) associated with �organic� illness like dementia, stroke, neurodegenerative disease and 2.) late-onset non-affective, non-organic psychoses

117. Very-late-onset Schizophrenia-like Psychosis (VLOSLP) The gross disturbances of affect, volition, and function characterizing schizophrenia are not prominent Nevertheless, paranoid delusions and hallucinations almost always occur. Often report plots against them, focusing on family members. Usually, cognitive impairment is not present. often report plots against them, focusing on family members. In contrast with mild suspiciousness, these plots are persistent, extreme, and elaborate. Usually, cognitive impairment is not present. often report plots against them, focusing on family members. In contrast with mild suspiciousness, these plots are persistent, extreme, and elaborate. Usually, cognitive impairment is not present.

118. Schizophrenia The prevalence of schizophrenia, as defined by the DSM-IV, is < 1% in the elderly True schizophrenia begins in adolescence or early adulthood and may persist into late life. New onset psychotic symptoms mandate thorough evaluation for etiology � metabolic, drug side-effect, etc.

119. Psychosis of AD Compared With Schizophrenia in the Elderly I First Rank Symptoms of Schizophrenia � Remembering Schneiderian First Rank symptoms is as easy as ABCD � A= Auditory hallucinations - 3rd person/echo-de-la-pens� B= Broadcasting of thoughts/ insertion/withdrawal C= Control experiences/ passivity phenomena D= Delusional perception First Rank Symptoms of Schizophrenia � Remembering Schneiderian First Rank symptoms is as easy as ABCD � A= Auditory hallucinations - 3rd person/echo-de-la-pens� B= Broadcasting of thoughts/ insertion/withdrawal C= Control experiences/ passivity phenomena D= Delusional perception

120. Psychosis of AD Compared With Schizophrenia in the Elderly II

121. Gradual Dose Reductions in Schizophrenia Some elderly patients who have had long-standing schizophrenia may no longer need antipsychotic treatment. At least one trial of discontinuation should be attempted but only when closely supervised

122. Psychosis in Parkinson�s Disease Visual hallucinations are the most common psychotic symptoms In some studies, more than 90% of all psychotic patients experienced visual hallucinations. Visual hallucinations are generally well formed, consisting of people or animals, and less commonly inanimate objects.

123. Psychosis in Parkinson�s Disease Hallucinations tend to occur during times of low ambient stimulation, most typically in the evening or when the patient is alone in a quiet environment. The hallucinations are present intermittently, lasting seconds to minutes at a time.

124. Psychosis in Parkinson�s Disease Delusions are commonly paranoid, consisting of beliefs about spousal infidelity or abandonment Psychotic symptoms generally occur 10 or more years after initial PD diagnosis. Earlier onset suggests Lewy Body Dementia, Alzheimer�s disease or other superimposed illness.

125. Depression in Parkinson�s Disease

126. Summary Biological advances in understanding psychiatric illnesses increasingly inform our management A measurement approach lets us use remission as a goal of treatment, and enables us to use dose titration, augmentation and switching in a more logical and effective way Simple to use measurement tools, particularly self administered ones, can be incorporated into every clinical encounter Tolerability, potential for drug-drug interaction, and safety profile should guide our choices amongst available treatment options Carmody et al J Affect Disord. 2006 Oct;95(1-3):115-8. Carmody et al J Affect Disord. 2006 Oct;95(1-3):115-8.

127. Summary The nursing home environment offers advantages (staff observation, assistance in using scales, etc) and disadvantages (limited access to non-pharmacologic interventions, Medicare Part D formulary hassles) Primary care physicians had best learn how to manage much of the psychiatric illness in SNFs, but also learn when to get help!