Depression - Phases of Treatment for Major depression: acute, continuation, maintenance

• Goals of Therapy:
• Acute: robust sustained response, reduce acute risk of suicide, provide agent with desirable pharm properties, adequate dosage and duration (9 to 12 mths)
• Continuation/Maintenance Therapy: minimize residual symptoms, improve long-term outcome, reduce likelihood of relapse and recurrence, restore occupational and psychosocial function, promote complance (simplified regimens, reinforcement of rationale, monitoring for confounding factors
• Duration of treatment with Antidepressants: determined by relapse rate
• Relapse rate: 1 episode Þ 50% chance of another relapse, 2 episodes Þ 65% of relapse, 3 episodes Þ 90% relapse rate (i.e. life long treatment)

• Treatment plan: psychotherapy is appropriate only for mild depression
• Misconceptions: depression is not a treatable disease, a weakness of character, antidepresant drugs cause dependence
• Life-style changes: not useful for significantly depressed patients
• Drug Choices:
• (1) Monoamine Oxidase inhibitors: phenelzine (Nardil), tranylcypromine (Parnate)
• (2) Tricyclic and heterocyclic Antidepresants (TCA’s): tertiary amines: imipramine (Tofranil), amitriptyline (Elavil), doxepin (Sinequan), trimipramine (Surmontil), clomipramine (Anafranil); secondary amines: desipramine (Srmontil), clomipramine (Anafranil)
• secondary = norepinephrine only; tertiary = serotonin and norepinephrine
• Advantages: established efficacy for acute/chronic use, inexpensive
• Disadvantages: slow onset (1-3wks), high risk in overdose (10day supply will kill you), drug interactions, side effects, 30% don’t respond, 30-40 fold variability in plasma levels, poor tolerance by elderly
• (3) Selective Serotonin Reuptake Inhibitors: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil)
• SSRI side effects: nausea, diarrhea, vomiting, sexual dysfunction (75%), restlessness, nervousness, tremulousness, insomnia, daytime drowsiness, headache Initial treatment: 75% are affected effectively
• Side Effects:

• Risk factors for recurrent depression: history of frequent and/or multiple episodes; double depression (major depression plus preexisting dysthymia (any mood disorder, minimum duration of 2 years), onset before 25 or after 60, long duration of individual episodes (average length 6-8 months therefore 2 years is long), severe index episode, seasonal pattern, family history of affective disorder, poor symptom control during continuation therapy, comorbid anxiety disorder or substance abuse
• Lifetime prevalence of mood disorder (20%): Every 1 in 5 people have a mood disorder

• Indications: psychotic depression, severe depression unresponsive to antidepressants, protracted mania, acutely suicidal patients, history of good response to ECT
• Contraindications: intracranial mass, untreated hyper- or hypo-kalemia
• Mechanism: seizure induced by ECT probably alters neuroreceptor levles and/or neuroreceptor activity in the brain
• Efficacy: 80% respond to therapy
• Pretreatment requirements: medical evaluation, informed consent
• Types of stimuli used: sine-wave - Medcraft, briefpulse - MECTA
• Electrode placement: unilateral vs. bilateral; average of 6-15 ECT treatment given per course
• Risks and side effects: risks from general anesthesia, memory impairment, post-ictal confusion, headaches

• Lithium Carbonate
• Indications: mania, prophylaxis for bipolar disorder, schizoaffective disorder, antidepressant augmentation
• Contraindications: severe deydration, renal disease, preganancy
• Mechanism: stalbilizes biogenic amine reuptake, MAO inhibition, serotonin
• Efficacy: 70% - manic patients; les effective for bipolar patients
• Pretrement evaluations: renal function, thyroid function, blood count, EKG
• Side effects: lithium toxicity (accidental or overdose)
• Anticonvulsants: Carbamazepine (Tegretol) and Valproate (Depakote)
• Indications: second line treatment for bipolar disorder
• Side effects: Carbamazepine: bone marrow suppression, agranulocytosis; Valproates: hepatotoxicity