Presentation on theme: "AFTER ALL, THERE IS NOTHING AS INTERESTING AS PEOPLE, AND ONE CAN NEVER STUDY THEM ENOUGH VINCENT VAN GOGH."— Presentation transcript:
AFTER ALL, THERE IS NOTHING AS INTERESTING AS PEOPLE, AND ONE CAN NEVER STUDY THEM ENOUGH VINCENT VAN GOGH
BIPOLAR DISORDERS Closely Kept Secrets New Treatments
EPIDEMIOLOGY OF BIPOLAR DISORDER Prevalence is underestimated at 1% Prevalence is probably 2% Calgary est. 2%x890000=17,800 citizens
COMORBID DISORDERS Substance Abuse – At least 61% Alcohol, Cocaine, THC Effect – More mixed and rapid cycling, poorer response to Lithium, slower time to recovery, and more lifetime hospitalizations Narcissistic PD Borderline PD 20-30% OCD, Panic Disorder
ADOLESCENCE Much more likely to be delusional and co morbid for substance abuse More likely to be irritable and misdiagnosed as conduct disorder
PRECIPITANTS 60% of first episodes precipitated by psychosocial, physical, or drug causes 30% of second episodes None of fourth episodes Illness starts as exogenous and becomes more endogenous Concept of kindling
SCREENING QUESTIONS Have you ever had a period of a week or so when you felt so happy and energetic that your friends told you that you were talking too fast or that you were behaving differently and strangely? Has there been a period when you were so hyper and irritable that you got into arguments with people?
SCREENING QUESTIONS Has anyone ever called you manic before?
DISTRACTABILITY Were you having trouble thinking or concentrating? Was this because things around you or even your thoughts were getting you off track?
INDISCRETION During the period we were talking about, how were you spending your time? Were you doing things that caused trouble for you or your family? Were you doing things that showed a lack of judgment, such as driving too fast, running red lights, or spending too much? Were you doing sexual things during this
INDISCRETIONS this period that was unusual for you?
GRANDIOUSITY During this period did you feel so confidant that you felt you could conquer the world? What was your best idea when you felt that way? Did you feel that you had special powers or abilities? Did you feel more religious than normal for you?
FLIGHT OF IDEAS During this period did you have so many thoughts, or were they so fast, that you could barely keep up to them? Did it feel like your thoughts were racing?
ACTIVITY INCREASE During that period, were you more active than usual? Were you constantly starting new projects and hobbies, working into the night?
SLEEP DEFICIT During that period, did you need less sleep? Did you ever stay up all night doing all kinds of things, like working on projects or phoning people? Did your sleep duration become reduced and still you had lots of energy?
TALKATIVENESS During this period, were you talking more than usual for you? Were you talking so much that people had to interrupt you to speak to you? Were you using the phone more than usual for you?
CORROBORATION Denial and lack of insight rule the day
TREATMENT OPTIONS Hospitalization for mania, severe depression Mood stabilizers, antipsychotics and antidepressants ECT – most effective treatment Supportive psychotherapy and CBT Lifestyle change Substance abuse treatment
LITHIUM CARBONATE 900 – 1500 mg/d mEq/L Most effective medication SEs include teratogenicity, tremor, renal dysfunction, acne, hypothyroidism, gastric upset, cardiac conduction problems, cognitive impairment Serum TSH, Cr, EKG, electrolytes pre and TSH, Cr q6mo. Mogen Schou rule, Always treat SEs
CARBAMAZEPINE 400 – 1000 mg/d Most effective for mixed states, rapid cycling SEs – sedation, ataxia, aplastic anemia, agranulocytosis Check CBC q3mo ?
VALPROATE 500 – 2000 mg/d; Highest blood level for effect. Highest dose is 60 mg/kg/d SEs – GI upset, weight gain, alopecia, teratogenicity, liver problems Best for mixed states, rapid cycling, secondary mania. Ineffective for depression Selenium for hair loss PCOD!
ATYPICAL ANTIPSYCHOTICS Olanzepine – mg/d; very effective; significant wt gain and lipid problems in some Risperdal mg/d; more EPS and increased prolactin in some Clozapine - For truly refractory patient, but can be remarkably effective. Slow response, serious SE profile and significant wt gain
Olanzepine Efficacy for Mania: Two Placebo-Controlled Studies Both double-blind, placebo-controlled, inpatient –Study I:3 weeks* –Study II:4 weeks** Olanzapine dosage: 5-20 mg/day –Starting daily dose:Study I- 10 mg Study II- 15 mg –Mean modal daily dose:Study I mg Study II mg DSM-IV Bipolar I Disorder, manic or mixed Lorazepam use limited to initial study phase *Study I -Tohen et al, Am J Psych 1999; **Study II- Tohen et al, XI World Congress of Psychiatry, Hamburg Germany, 1999
Olanzepine Grp. Superior YMRS Scores Y-MRS Total score designated a priori as primary outcome measure. *p=0.02, **p<0.001; LOCF Study I three weeks Study II four weeks Baseline : n=70n=66n=54n=56 * ** Mean Change to Endpoint (LOCF)
Antimanic Efficacy of Olanzapine Is Significant Starting at the First Assessment (Week 1 Y-MRS) Placebo Olanzapine 1 * * * * * p <.05. Response curve illustrates four week study of olanzapine (n=54) vs placebo (n=56) for acute mania (four week study II) 15 mg starting dose Week of Study 234 Percent Change from Baseline in Y-MRS Total
Similar Y-MRS Improvement in Non-Psychotic and Psychotic Subjects *p=0.88; **p=0.41. No difference in mania improvement among olanzapine- treated subjects with and without psychotic features Mean Change (LOCF) Study I three weeks Study II four weeks ** * Non-psychotic Psychotic Baseline :
There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement, four-week study II) between olanzapine-treated patients in manic or mixed episodes (p=.681) Y-MRS Total: Manic vs Mixed Episodes Mean Change Manic episode n=31 Mixed episode n=23 Baseline: Study II four weeks
In Patients Presenting with Depressive Symptoms HAMD Improved During Olanzapine Treatment In patients with depressive symptoms, olanzapine-treated patients had a statistically significantly greater mean improvement in HAMD 21 total scores compared to placebo-treated patients in this four-week study II acute mania trial. *p=0.046 HAMD 21 total score 20 at baseline Baseline: n=21 * Olanzapine Placebo Mean Change in HAMD 21 Total
Mean Change There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement, four-week study II) between olanzapine-treated patients with history of good vs poor response to lithium treatment for mania (p=.641) Responder n=18 Non-responder n=24 Most Recent Lithium Response: Y-MRS Total: Lithium Responders vs Non- Responders Baseline: Study II four weeks Baker RW et al. Bipolar Disorders Conference. Phoenix, Arizona, January 2000.
Y-MRS Total: Valproic Acid Responders vs Non-Responders There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement, four-week study II) between olanzapine-treated patients with history of good vs poor response to valproate treatment for mania (p=.546) Mean Change Baseline: Study II four weeks Responder n=11 Non-responder n=21 Baker RW et al. Bipolar Disorders Conference. Phoenix, Arizona, January 2000 Most Recent Valproic Acid Response:
Treatment-Emergent Adverse Effects During Acute Mania Trials These four events were the only ones significantly more common (p<0.05) in olanzapine-treated subjects Event% Reporting Placebo (n=129) Somnolence Dry mouth Dizziness Asthenia 35% 22% 18% 15% 13% 7% 6% Olanzapine (n=125)
Persisting Improvement in Depression Ratings During Extended Olanzapine Treatment Mean Change in HAMD 21 Total Score (LOCF) A significant improvement in depressive symptoms as measured by the HAMD 21 was observed from baseline (12.17) to endpoint (mean change = -5.77, p<.001). Tohen MF et al, European Neuropsychopharmacol 9(Suppl5):S247, 1999 Weeks of Open-Label Therapy
GABAPENTIN Anticonvulsant, least effective new drug Most helpful with anxiety, insomnia, pain May cause persistent sedation Excreted by kidneys only, no drug interaction 1200 to 4000 mg/d.
LAMOTRIGINE Anticonvulsant, best for Bipolar depression Improved cognition, excellent tolerance, serious autoimmune rash Valproate interaction 12.5 to 25 mg/wk increments. Dose range of 75 to 300mg/d.
TOPYRAMATE May augment other medications? Significant cognitive ill effect and paresthesiae BUT SIGNIFICANT WEIGHT LOSS, AND NEVER UNDERESTIMATE LOOKING GOOD !!!!!! 50 mg qhs, increase by 50 mg/wk. in divided doses to maximum of 200 mg bid
THYROID AUGMENTATION TSH is not reliable indicator of subclinical hypothyroidism in mood disorder patients T3 and T4 in lower range of normal cause cognitive impairment, relapse and lethargy Supplemental T4 caused 10/11 Li refractory to respond Large study showed no bone density effect of high dose T4 treatment
NEVER GIVE UP It will help patient to be inspired by us, rather than the other way around