3. ANTI-DEPRESSANTS

11. SINGLE NEUROTRANSMITTER ADDRESSED SEROTONIN

14. SSRIs EFFICACY vs. SAFETY = TCAs >TCAs

16. SINGLE RECEPTOR SELECTIVITY SEROTONIN-REUPTAKE INHIBITORS/ RECEPTOR BLOCKERS TRAZODONE NEFAZODONE

17. EFFICACY vs SAFETY =TCAs >>TCAs

21. EFFICACY vs SAFETY ( =/>?TCAs (>>TCAs)

23. MOOD STABLIZERS

26. EFFECTIVENESS OF POSSIBLE MOOD STABLIZERS Acute Acute Acute Maint- Mania Mixed Rapid enance States Cyclers Lithium Yes No? No? Yes Valproate Yes Yes Yes Yes Carbamazepine (Yes) Yes Yes Yes Olanzapine/ Yes Yes Yes Pending* Clozapine * Open extension data positive for olanzapine

28. PRECIPITATION OF MOOD EPISODES Mania Depression Lithium No No Valproate No No Carbamazepine No No Olanzapine/ No No Clozapine Antidepressants Yes No Typial antipsychotics No Probable

29. EASE OF USE OF MOOD STABILIZERS Simple Frequent Lab Prescribing Monitoring Lithium No Yes Valproate Somewhat Somewhat Carbamazepine No Yes Olanzapine/ Yes No Clozapine No Yes

30. SIDE EFFECTS OF MOOD STABILIZERS Lithium Weight gain, tremor, Gl symptoms,  thyroid function, cognitive complaints Valproate Weight gain, (  thyroid function), Gl upset, pancreatitis, ? Polycystic ovaries Carbamazepine  WBC, rashes, nausea Olanzapine/ Weight gain, sedation ? Hyperglycemia Clozapine Weight gain, sedation, agranulocytosis,  salivation, ? hyperglycemia

32. PUTATIVE/INNOVATIVE MOOD STABILIZERS FOR REFRACTORY BIPOLAR PATIENTS Anticonvulsants Ca2+Channel Blockers Gabapentin Verapamil Lamotrigine Nifedipine topiramate Nimodipine Tiagabine Acetazolamide

33. Atypical Antipsychotics Hormonal Clozapine thyroxine Risperidone Estrogen/progesterone Olanzapine Tamoxifen Quetiapine (Ziprasidone) Other Tryptophan Choline Donepezil Omega-3 fatty acids PUTATIVE/INNOVATIVE MOOD STABILIZERS FOR REFRACTORY BIPOLAR PATIENTS

36. Lithium Divalproex Carbamazepine First Line Lamotrigine ? Gabapentin Olanzapine Topiramate Efficacy in Depression Clinical Features ?

54. Rapid cycling 10 – 20% Mixed (dysphoric) 30 – 50% Pure mania 30 – 50% VPA VPA Li, VPA Olanz, VPA ? GB BP II Dep Lamotrigine Not listed in DSM IV TR. Anxiety, Hostility, Impulsivity, Poor insight, Confusion, Memory impairment Sensory hyper acuity Mania with psychotic Features 25 – 75% Mood Stabilizer Combinations Phenomenological Domains

55. ANTI-ANXIETY DRUGS

58. BENZODIAZEPINES A FRIEND FOE ? OR

59. History of Anxiolytic Development ALCOHOL 1903 - BARBITURATES 1950’s – NON BARBITURATES (Meprobamate) LATE 50’s - BENZODIAZEPINES NONBENZODIAZEPINE HYPNOTICS GABA MIMETICS SELECTIVE GABA A TARGETS

82. BZD-2 receptors (Omega-2) - caudate putamen, olfactory bulb, cerebral cortex, hippocampus and dentategyrus Related to cognitive, memory and psychomotor function. BZD-3(Omega-3) are not directly associated with GABA receptors or with chloride channels . They may regulate the synthesis of neuroactive steroids. BENZODIAZEPINE RECEPTOR

83. BDZ GABA Cl Channel GABA BENZODIAZEPINE RECEPTOR

85. GABA RECEPTOR

86. GABAergic System Morris B et al (2005) Current Opinion in Pharmacology 5 : 101 - 106  2 CCK/VIP+  1

87. GABAergic System

91. The most deserving six-letter word....... “ THANKS" for your patient listening.