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A. Typesnavigator

  1. Organic (Organic Brain Disease)
    1. Delirium
    2. Korsakoff's Syndrome
  2. Psychiatric
    1. Schizophrenia
    2. Major Affective Disorders (Bipolar and Unipolar)
    3. Manic-Depressive Illness (MDI) - Bipolar Disorder
    4. Unipolar: Major Depressive Disorder (MDD) or Psychotic Depression
    5. Brief reactive psychosis
    6. Delusional Diseases
    7. Abnormalities in various grey matter brain regions associated with psychosis [10]
  3. Tourette's Syndrome (see below)

B. Occurrencenavigator

  1. Some family history in many of these illnesses
  2. Treatment
    1. All of the psychoses usually respond to drug therapy
    2. Dementia and Korsakoff's Syndrome cannot be reversed; treat with anti-pscyhotics
    3. Delirium often due to drug effects or underlying disease
  3. ~5% of population suffer from non-MDI psychoses
  4. Cannibus (marijuana) use at any time associated with 1.4X increased risk of any psychosis [1]

C. Schizophrenia navigator

  1. Affects ~1% of population in USA
  2. Positive (delusions, hallucinations) and negative (flattened affect) symptoms
  3. Usually begins in adolescence or early adult life
  4. Appears to be related to abnormal dopamine regulation in the brain
  5. Choice of Antipsychotic Agent [11,12,13]
    1. Atypical (newer) agents are generally recommended first line over typical antipsychotics
    2. Atypical agents cause less extrapyramidal side effects (EPS) and treatment discontinuations are less than for haloperidol (first generation) [19]
    3. Olanzapine has the best compliance rates amongst patients with 64% discontinuation rates at 18 months versus 74-82% for respiridone, perphanzine, quetiapine, ziprasidone
    4. Risperidone had lowest rate of treatment discontinuation due to side effects (10%) versus olanzapine which ahd highest rate of discontinuation due to side effects (18%)
    5. Olanzapine was discontinued usually for weight gain and metablic effects
    6. Perphenazine (first generation antipsychotic) discontinued for extrapyramidal effects
    7. Aripiprazole and clozapine were not included in the discontinuation study
    8. Clozapine is probably the most effective but is for refractory disease due to side effects
    9. Perphenazine has lower potency and reduced side effects compared with haloperidol
  6. Relative Efficacy of Atypical Antipsychotics [13]
    1. Clozapine (Clozaril®) ++++
    2. Olanzapine (Zyprexa®) +++
    3. Risperidone (Risperdal®) +++
    4. Quetiapine (Seroquil®) ++
    5. Ziprasidone (Geodin®) ++
    6. Aripiprazole (Abilify®) ++
  7. Weight gain with Antipsychotics [18]
    1. Lifestyle intervention and metformin (750mg/day) alone and in combination reduce antipsychotic induced weight gain
    2. Metformin alone reduced BMI 1.2kg/m2, lifestyl intervention alone reduced BMI 0.5kg/m2
    3. Combination of metformin + lifestyle intervention reduced BMI 1.8kg/m2
  8. Risk of Death in Elderly Patients [14,15,16]
    1. Atypical antipsychotics may have increased risk of death in elderly patients [14]
    2. Conventional antipsychotics have at least as high, if not ~35% higher, risk of death than newer agents in elderly patients with behavioral disturbances [15,16]
    3. More recent epidemiological review shows a 1.3X overall increase and 1.67X increase with high dose for use of conventional versus atypical antipsychotics in the elderly [8]
    4. Atypical antipsychotics appear to be safer than conventional agents in elderly

D. Mania navigator

  1. Symptoms
    1. Irritability, euphoria, delusions (grandiose)
    2. Rapid speech, flight of ideas, pressured speech
    3. Decreased sleep, increased appetite, increased sexual drive
    4. Increased distractability
    5. Increased activities, usually with hightened risk potential
  2. Acute Therapy
    1. Antipsychotic Agents - haloperidol (Haldol®) and others
    2. Electroconvulsive Therapy (ECT) - only for acute mania
    3. Benzodiazepines in high dose - clonazepam (Klonopin®) or lorazepam
  3. Maintenance Therapy (in usual order of preference) [2,5]
    1. Lithium
    2. Valproate - probably as effective as lithium [4]
    3. Carbamazapine (Tegretol®)
    4. Neurontin, Lamotrigine

E. Bipolar Disorder [3] navigator

  1. Most patients mania will also have bouts of depression
  2. Depression without mania is the most common Affective disorder
  3. Therapy Overview
    1. Depends on components and severity
    2. Mood Stabilizers are mainstay of therapy
  4. Mood Stabilizers [5]
    1. Valproate [4]
    2. Carbamazepine
    3. Lithium
    4. Anti-depressant should be added only if patient is severely depressed

F. Tourette's Syndrome [6,7] navigator

  1. Probable genetic disease
    1. Diagnosis requires onset by age 21
    2. 96% of cases diagnosed by age 11
  2. Components
    1. Uncontrollable facial and whole body tics and/or phonic tics
    2. Obsessive compulsive disorder (OCD)
    3. Attention deficit hyperactivity disorder ADHD)
    4. Other behavioral disorders (particularly impulse control)
    5. Family history of similar symptoms
  3. Treatment is based on symptoms
    1. Tics treated with dopamine receptor blockers (neuroleptics)
    2. Clonidine or guanfacine for impulse control (also for ADHD), and some activity for tics
    3. Clonidine or guanfacine (alpha2 adrenergic agents) less effective but less toxic than dopemine receptor blockers
    4. Stimulants for ADHD
    5. Serotonergic drugs for OCD
  4. Recommended Dopamine Receptor Blockers
    1. Typical Neuroleptics: Haloperidol, Fluphenazine, Sulpiride, Trifluoperazine
    2. Atypical Neuroleptics: Risperidone, Ziprasidone
    3. Transdermal nicotine potentiates effects of haloperidol
  5. Serotonergic Drugs for OCD
    1. Fluoxetine
    2. Clomipramine
    3. Sertraline
    4. Paroxetine
    5. Fluvoxamine
    6. Venlafaxine
  6. Tic Disorders in Childhoold [9]
    1. Autoimmune etiology probably due to molecular mimicry has been postulated
    2. Streptococcal infections associated with obsessions and Tic disorders in children
    3. ß-hemolytic streptococci cross-react with neuronal cells leading to CNS inflammation
    4. Similar pathophysiology may be found in Sydenham's Chorea
    5. Improvements 30-50% with intravenous immunoglobulin or plasma exchange reported

G. Other Disordersnavigator

  1. Depression with psychotic features
  2. Delusional Disease
    1. Usually in elderly patients
    2. Isolated delusions
    3. Patients usually function well otherwise
    4. Difficult to treat
  3. Brief Reactive Psychosis
  4. In intellectually disabled patients with aggressive challenging behavior, risperidone or haloperidol are no better than placebo on controlling behavior [17]

References navigator

  1. Moore TH, Zammit S, Lingford-Hughes A, et al. 2007. Lancet. 370(9584):319 abstract
  2. Treatment of Psychiatric Disorders. 1994. Med Let. 36(933):93
  3. Muller-Oerlinghausen B, Berghofer A, Bauer M. 2002. Lancet. 359(9302):241 abstract
  4. Valproate. 1994. Med Let. 36(929):74 abstract
  5. Treatment of Psychiatric Disorders. 1997. Med Let. 39(998):38
  6. Jankovic J. 2001. NEJM. 345(16):1184 abstract
  7. Leckman JF. 2002. Lancet. 360(9345):1577 abstract
  8. Schneeweiss S, Setoguchi S, Brookhart A, et al. 2007. CMAJ. 176(11):627
  9. Perlmutter SJ, Leitman SF, Garvey MA, et al. 1999. Lancet. 354(9185):1153 abstract
  10. Pantelis C, Velakoulis D, McGorry PD, et al. 2003. Lancet. 361(9354):281 abstract
  11. Lieberman JA, Stroup TS, McEvoy JP, et al. 2005. NEJM. 353(12):1209 abstract
  12. Choice of Antipsychotic. 2004. Med Let. 45(1172):102
  13. Second Generation Antipsychotics. 2005. Med Let. 47(1219):81 abstract
  14. Kuehn BM. 2005. JAMA. 293(20):2462' abstract
  15. Wang PS, Schneeweiss S, Avorn J, et al. 2005. NEJM. 353(22):2335 abstract
  16. Gill SS, Bronskill SE, Normand ST, et al. 2007. Ann Intern Med. 146(11):775 abstract
  17. Tyrer P, Oliver-Africano PC, Ahmed Z, et al. 2008. Lancet. 371(9606):57 abstract
  18. Wu RR, Zhao JP, Jin H, et al. 2008. JAMA. 299(2):185 abstract
  19. Kahn RS, Fleischhacker WW, Boter H, et al. 2008. Lancet. 371(9618):1085 abstract