DEPRESSION AND ANTIDEPRESSANT DRUGS

I. Behavioral Characteristics
    A. Clinical Depression: an “affective” or mood disorder
        1. Important diagnostic parameters: length of disturbance, dysphoria, no obvious situational trauma, thoughts of suicide, degree to which disorder impairs ordinary function and quality of life
        2. Increased risk of suicide
        3. Distinguishing bipolar from unipolar depression:
        4. Treatment must address episodic symptoms AND relapse.
    B. Dysthymia: similar symptoms, although less intense and more enduring
        1. Degree of functional impairment is often the measuring stick for diagnosis.
        2. Comorbidity:
    C. Acute Situational Grief / Stress

II. Tricyclic Antidepressants (TC)
    A. TCs are still the treatment standard.
        1. Newer drugs are not more effective, just have different side-effect profiles.
        2. Clinicians must match a client to a drug efficacy and drug side-effect profile.
        3. TCs do not produce psychological or physiological dependency.
    B. Behavioral effects in clinically depressed individuals appear gradually.
    C. Side-effects: anticholinergic, cardiotoxicity, antihistamine
        1. Prominent sedative effects on very young or elderly
        2. Indirect effects may offset direct effects.
    D. Neural mechanisms of action:
        1. Depression is NOT the outcome of a simple reduction of neurotransmitter(s).
            a. Evidence: time courses (neural differs from behavioral), psychostimulants are not therapeutic
            b. TCs, SSRIs do NOT bind to postsynaptic 5-HT receptors.
        2. Blocking reuptake of NE and / or 5-HT -> more neurotransmitter available -> excessive postsynaptic receptor stimulation -> neural system “adjustment” -> postsynaptic receptor desensitization -> ?
            a. In the depressed, TCs might bind to “overactive” presynaptic receptors.
    E. Sites of action of the TCs are unknown.
    F. Pharmacokinetics:
        1. Some members of class have active metabolites.
        2. Cross placenta but have low incidence of fetal effects.