TREATMENT OF DEPRESSION EFFICACY OF ANTIDEPRESSANTS: 65% OF PATIENTS TREATED WITH A GIVEN ANTIDEPRESSANT IMPROVE 30% IMPROVE SPONTANEOUSLY OR WITH PLACEBO MATCHING DRUGS TO CONDITIONS: MAJOR DEPRESSION The clinician must experiment! Clearly best to begin with drugs low in side-effects! ATYPICAL DEPRESSION (HIGHLY VARIABLE MOOD) MAOI often preferred to TCAs DELUSIONAL DEPRESSION Antidepressant alone is ineffective Antidepressant plus neuroleptic often works ECT probably best BIPOLAR DEPRESSION All antidepressents may trigger mania (bupropion is safest) MAOIs better than TCAs Lithium the drug of choice, except for profound mania Lithium + MAOI or Li + carbamazepine (an anti- epileptic) often good in refractory cases DYSTHYMIA Antidepressants LESS helpful than in major depression! MAOIs preferred to TCAs SSRIs still under study GERIATRIC DEPRESSION Drug choice based on side-effect profile Reduced side effects: desipramine, nortriptyline, SSRIs, bupropion USE LOWER DOSES COMORBID DISORDERS: Panic disorder: bupropion, trazadone ineffective TCAs helpful when agitation/insomnia present Obsessive-Compulsive disorder: SSRIs drug of choice Eating disorders: Lowered intake responds to TCAs, over-eating to SSRIs DRUG COMBINATIONS FOR TREATMENT-REFRACTORY DEPRESSION DUAL DRUG COMBINATIONS: lithium augments most antidepressants Imipramine + fluoxetine often helpful As is the SSRI + bupropion combo BUT BEWARE SIDE-EFFECTS! REFRACTORY DEPRESSIONS OFTEN RESPOND TO ECT THYROID (T3) AUGMENTATION OF ANTIDEPRESSANTS, ESPECIALLY TCAs STIMULANTS (METHYLPHENIDATE) AUGMENT ANTIDEPRESSANTS TREATMENT OF PSYCHOSES MORE ABOUT SCHIZOPHRENIA: NOSOLOGY POSITIVE AND NEGATIVE SYMPTOMS: Positive symptoms include: + Delusions + Hallucinations + Disorganized speech and behavior + Agitation Negative symptoms include: + Blunted affect/anhedonia + Social withdrawal + Passivity/apathy, lack of volition + Reduced verbal fluency DIAGNOSTIC CATEGORIES Hebephrenia or "disorganized" schizophrenia + Typically early onset + Negative symptoms predominate + Inappropriate laughter and silliness sometimes seen + Bleak prognosis: the "bag ladies" are typically hebephrenic Paranoia + Often relatively sudden onset + Paranoids are relatively more intact, less withdrawn than are other schizophrenics + Delusions of grandeur, persecution and reference dominate the clinical picture + Often accompanied by vivid hallucinations + More prone to violence than other forms Catatonia: + Common in the past, now rare + Involves long periods "frozen" into often bizarre positions + Often interspersed with brief periods of hyper- excitation, frenzied and sometimes assaultive behavior "process" vs "reactive" schizophrenia "Process" schizophrenia often hebephrenia: relative early onset, negative symptoms predominate, long downward course, poor prognosis "Reactive" schizophrenia often paranoid: sudden onset in mid-twenties or later, accompanied by positive symptoms including pronounced delusions and hallucinations, with a relatively good prognosis RELATED DISORDERS Polydipsia (around 20 % incidence) Deficits in control of the eyes: + Smooth pursuit deficits + Reduced rate of blinking + Abnormal saccades "soft" neurological signs, especially movement abnormalities Cigarette smoking (70% smoke) Attentional deficits EEG deficits: P300 visual-evoked response is disrupted Pre-pulse inhibition of auditory startle impaired A "prefrontal" profile on psychological tests Memory problems MORE ABOUT SCHIZOPHRENIA: EPIDEMIOLOGY PREVALENCE: Hard to determine, since many schizophrenics live on the street Estimated at 0.5 to 2 % in US, depending in part on definition 25% of all hospital beds in US occupied by schizophrenics 40% of all long-term care days involve schizophrenia GENETICS around 1/3rd of monozygotic twins are concordant + around 18% of the OFFSPRING of non- schizophrenic monozygotic twins are schizophrenic 6 % of dizygotic twins are concordant In adopted children with schizophrenic mothers: + 16.6% later develop schizophrenia + Mental retardation rates and crime also up! In adopted children who develop schizophrenia, schizophrenia is 10-fold higher in biological than in adopted relatives Biological relatives of schizophrenics are more likely to show "soft signs" of schizophrenia, including clumsiness, eye movement abnormalities, suspicion and thought disorders THE SEARCH FOR SCHIZOPHRENIC GENES Various studies have identified four separate "schizophrenic" genes. None of these findings has been successfully replicated! No genetic abnormalities have been found in genes for the D1 through D5 dopamine receptors SEX DIFFERENCES Incidence is about the same for men and women There is a minor peak in late schizophrenia in women around menopause Typically, men develop schizophrenia earlier than women Male schizophrenic symptoms are more severe and more chronic than for women Women schizophrenics are more likely to have schizophrenic relatives - indicating that women need more "risk factors" to develop schizophrenia VIOLENCE: One in five schizophrenics will commit suicide One in ten schizophrenics will attack someone CAUSAL ENVIRONMENTAL FACTORS: The "viral" hypothesis: + Urban residence in childhood + Crowded living quarters + Presence of older siblings + Seasonal effects: 8% more likely in children born in late winter, but ONLY if born in urban areas! + Influenza in the second trimester predisposes BUT other complications of pregnancy also predispose AS do other problems. In Holland, schizophrenia went up 13% in pregnancies during the 1940 German invasion, and 50% after the "Hunger winter" of 1944