Anxiety

Severity in Mood Disorders

Jan Fawce6, M.D. The University of New Mexico School of Medicine

Moderate severity anxiety. 62% of patients with major depression were found to have moderate anxiety by SADS-C. Primary> Secondary, Endogenous> NonEndogenous, Unipolar = Bipolar Fawcett J and
Kravitz, 1983

The Frequency and Severity of Anxiety in Major Affective Disorders

The severity of anxiety symptoms should be clinically assessed.

Distribution of Anxiety Summary Score

in 327 Unipolar Depressives Clayton P et al 1991

30

25

20

15

10

0
6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Raw Score

Adapted from Clayton PJ et al. Am J Psychiatry. 1991;148:1512-1517.

Baseline Total (8 symptoms) Anxiety Severity and Subsequent Time Spent in Depression over 25 Years

ProspecLve Study Findings- Standard Risk Factors May Not Predict Acute Risk, but Chronic Risk-
Fawce6 et al,1990

954 major affective disorder (>80% hosp) First year follow up- 13/34 suicidesstandardized measures: no significant difference between 13 suicides and 951 surviving: 1.Severity of Suicidal Ideation2.Hx Suicide Attempts (past and recent) 3.Severity of Hopelessness Years 2-10 - significant correlation with suicide (34) compared with non-suicides

Acute Risk Factors Fawcett et al, 1990

Significantly more severe or frequent in suicides occurring weeks up to a year of follow up: Severity Psychic Anxiety( intensity + pervasiveness ) Panic Attacks Global Insomnia ( initiating, middle waking, early waking ) Severity Anhedonia Alcohol Abuse ( moderate-recent onset ) Agitation (depressive turmoil)/ including mixed dysphoric mania Treatment Modifiable Symptoms

100 Cases of Severe Suicide A6empts

Hall et al, 1999

90% severely anxious month before 80% panic attacks before 92% insomnia-46% global insomnia 84% saw MHP in past month 83% no harm contract 68% alc/SA 69% fleeting SI-no threats 78% relational conflict

Inpatient Suicide - Clinical Features Within 1 Week n=76

Busch K. et al, J Clin Psych 2003

Severe Anxiety (SADS-C 5-6) Severe Agitation Both Severe Anxiety+Agitation Either/Both Anxiety/agitation (SADS-C <5) Denial of Suicide Ideation No harm contract

30% 10% 39% 79% 22% 76% 26%

Anxiety as a Suicide Risk Factor in Depressed Veterans Pfeiffer PN et al, Depress Anxiety 2009
887,859 patients with depression Odds of suicide significantly increased in PD, GAD, Anx Nos (OR 1.25-7) Decreased in PTSD, no relationship with OCD,SP and others. Odd of suicide greater in patients receiving anti-anxiety medication (OR 1.71) and higher in those receiving high dose anti-anxiety medication (OR 2.26) Emphasize importance of co-morbid anxiety disorders and symptoms in increasing suicide risk in depressed patients. Suggests a relationship with anxiety severity It appears treatment of anxiety was not very effective with benzodiazepines and buspirone..

Nock Model of Suicidal Behavior

al, PLoS Med, 2009

Nock et

Cross-national analysis of association among mental disorders and suicidal behavior:WHO World Mental Health Surveys 108,664 respondents from 21 countries. Strongest predictors of SB in developed counties mood disorders, in undeveloped countries impulsecontrol disorders Large number of disorders predict suicide ideation only disorders characterized by anxiety and impulse control disorders predicted suicidal behaviors in both developed and developing countries. ( BD. BPD, SADD) Model: Low mood Suicidal Ideation. Plus increased anxiety/impulsiveness leads to Suicidal Behavior

DSM-5 Anxiety Scale adapted from PROMIS measure

Anxious Symptoms: 1. Feeling keyed up and tense 2. Feeling unusually restless. 3. Trouble concentrating because of worry. 4. Fear that somehting awful may happen 5. Feels that individual may lose control. Two or more of above symptoms majority of days: Anxious Distress

Scoring of DSM-5 Anxiety Specifier Scale

Anxious Distress specifier: defined as 2 or more of anxious symptoms for majority of days. Clinical Anxiety Scale: 0. Not Anxious 1.Mildly anxious 2.Moderate anxiety-2 symptoms 3.Severely Anxious- 3-5 symtoms 4.Severely Anxious with motor agitation

Nu6, 2007

Double Breaching Humpbacks 2013

Whose Dopamine Tone is Higher?

TRMD paLent 2-KH

History of chronic depression for 13 years. History of manic and mixed episodes-last episode 2 yrs ago. History of alcohol, cannabis, and methedrine abuse- but not for 14 years. Hospitalized 5 Lmes- last 2 years ago Suicidal ideaLon- no a6empts Mother bipolar, maternal aunt bipolar, father alcoholic Since 1983- severely disabled

TRMD- KH- Past Treatment

-Two past courses of ECT 10 RX, 12 Rx. No help Tranylcypromine (Parnate) 60 mg 9 years(up to 180 mg) Failed 3 SSRIs, Mirtazapine, Venlafaxine, Lamictal 175 mg, Tegretol 1000 mg, Ritalin, Modafanil no help. Lithium 1200 mg, sLll depressed. In bed all day, lives alone, has a male friend.

KH-Present Treatment

7/05 Parnate up to 100 mg- - no help 9/05 Seroquel up to 600 mg. 10/5 AugmentaLon with Nortriptyline 100 mg, Dexedrine 20 mg bid no help Now What?

KH- EecLve Treatment

1/06 Clomipramine up to 250 mg mood improved 3/06 recurrence of depression- Seroquel 100 mg 5/06 o CMI 5 days, switch to Nortriptyline-) depression increased----.Selegiline (Ensam patch 12 mg- Now depression worse than in 14 years Course of 12 ECT no help Back to Clomipramine- 250 mg.- this Lme depression stabilized Goes ahead with VNS implantaLon.

KH-EecLve Treatment
11/06 CMI 250-300 mg. 1/07 depression stabilized has VNS implant. 2/07 moderate depression 3/07 CMI 300 mg/VNS remi6ed 5/07 feels withdrawn- add Abilify 5-15 mg- improved 8/09 remi6ed 11/09 depression recurring on CMI 250 mg,Lithium 900 mg, Seroquel 200 mg, VNS

KH EecLve Treatment
1/10 SLll Depressed- Pramipexole (Mirapex) 1.0 3.0 mg. added Tired added Dexedrine 10 bid 3/10 improved 6/11 be6er than in 14 years CMI 225 mg., Mirapex 3.0 mg, Dexedrine 10 mg Ld., VNS- - no hypomanic or mixed episodes. Had some recurrence of decreased energy reversed with increase of Pramipexole to 4.0 mg. Turned out to be related to cirrhosis of liver.

Summary
Clear evidence is presented that comorbid severe anxiety is associated with poorer clinical outcomes and suicide risk across mood disorders. A signicant porLon of this evidence iniLally emerged from the CDS. This has led to the addiLon of an Anxiety Specier that focuses a6enLon on the importance of Comorbid Anxiety Severity in DSM-5 across all Depressive and Bipolar Disorders. May promote dierenLal treatment.