2. 1. Fawcett J, Barkin RL. J Clin Psychiatry . 1997; 58(Suppl 6): 32 â 39. 2. O'Reardon JP, Amsterdam JD. Psychiatr Ann 1998; 28: 633 â 640. Approximately 2/3 of patients treated for depression will fail to achieve remission (HAM-D †7) 2
3. 1. Paykel ES, et al. Psychol Med 1995; 25: 1171 â 1180. Patients were interviewed at 3-monthly intervals according to the Clinical Interview for Depression and HAM-D 17 Rating Scale Depressed patients with unresolved symptoms are 3 times more likely to relapse 1
6. Treatment aims Complete symptom resolution Return to premorbid functioning (psychosocial, occupational) The maintenance of normality The prevention of recurrence
7. Limbic System Prefrontal Cortex Locus Coeruleus (NA source) Raphe Nuclei (5-HT source) Amygdala Hippocampus Cooper JR, et al. The Biochemical Basis of Neuropharmacology . 8th ed. New York: Oxford University Press; 2003. Descending 5-HT pathways Descending NA pathways
10. ACUTE MECHANISM OF ACTION UNDESIRABLE PHARMACOLOGICAL ACTIONS TCAs Anticholinergic; antihistaminic; alpha1 adrenoceptor blockade; direct membrane stabilisation SSRIs Citalopram(Cipromil), Fluoxetine (Prozac), Fluvoxamine(Faverin), Paroxetine(Seroxat), Sertraline (Lustral) 5-HT re uptake inhibition MAOIs Phenelzine(Nardil), Isocarboxazid(Marplan) Tranylcypromine(Parnate) Inhibition of MAO-A and MAO-B isoenzymes Interaction with tyramine and sympathomimetic drugs; Irreversible and non-selective inhibition of MAO isoenzymes RIMAs Moclobemide(Manerix) Reversible Inhibition of MAO-A SNRIs Venlafaxine(Efexor) Duloxetine(Cymbalta) 5-HT and NA re uptake inhibition Reboxetine(Edronax) NA re uptake inhibition Mirtazapine(Zispin) Alpha2 adrenoceptor blockade 5-HT2 receptor blockade
32. First generation Second generation Weight gain Hyperglycaemia, diabetes Insulin resistance Cardiovascular dis Dyslipidaemia Less EPS Less QT prolongation Less hyperprolactinaemia Neurological side effects EPS Tardive dyskinesia Hyperprolactinaemia
While treatment for depression has evolved over the decades and side-effect profiles and interaction profiles have improved dramatically compared with those known to be associated with monoamine oxidase inhibitors and tricyclic antidepressants (TCAs), much work remains to be done In response to treatment of first choice, a significant proportion of patients fail to reach acceptable levels of function and well-being In short-term, placebo-controlled clinical trials, about a third of patients achieve partial or no response 1 and only about a third achieve remission 2 References Fawcett J. Barkin RL. Efficacy issues with antidepressants. Journal of Clinical Psychiatry 1997; 58 (Suppl 6): 32 â 39. O'Reardon JP, Amsterdam JD. Treatment-resistant depression: progress and limitations. Psychiatric Annals 1998; 28 : 633 â 640.
The presence of residual symptoms of depression was associated with a relapse rate of 76% compared with a relapse rate of 25% among patients who did not have residual symptoms Reference Paykel ES. Ramana R. Cooper Z. Hayhurst H. Kerr J. Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychological Medicine 1995; 25 (6): 1171 â 1180.
The objectives for the treatment of depressed patients are to: Achieve remission (acute treatment) Prevent relapse (continuation treatment) Prevent recurrence (maintenance treatment) 1 A response is defined as a 50% improvement in symptoms as measured by the HAM-D score 2 Remission is a virtually symptom-free state â the HAM-D score is †7 3 Relapse is a worsening of symptoms after remission 1 Recurrence is the development of a new episode after initial recovery 1 The risk of relapse is significantly higher in patients that respond only partially to therapy compared with those who achieve remission (76% versus 25%) 4 Reference 1. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991; 52 (5, Suppl):28â34. 2. Fawcett J, Barkin RL. Efficacy issues with antidepressants. J Clin Psych 1997; 58 (suppl 6):32â38. 3. Ballenger JC. Clinical guidelines for establishing remission in patients with depression and anxiety. J Clin Psych 1999; 60 (suppl 22):29â34. 4. Paykel ES. Ramana R. Cooper Z. Hayhurst H. Kerr J. Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychological Medicine 1995; 25 (6): 1171 â 1180.
KEY POINTS: Both serotonin (5-HT) and noadrenaline (NA) are neurotransmitters that have ascending tracts to the cerebral cortex and limbic area, as well as descending tracts to the spinal cord 1 The cell bodies for these tracts originate in major nuclei of the midbrain. For the central nervous system, the 5-HT cell bodies are located in the raphe nuclei and the largest cluster of NA cells are located in the locus coeruleus 1 Each of these midbrain nuclei has ascending tracts, which project to brain regions thought to be involved in depressive symptoms, as well as ascending and descending tracts involved in pain suppression The monoamine theory of depression suggests that a relative deficiency in synaptic levels of serotonin and noradrenaline in key central nervous system pathways underlies depressive illness (CNS = brain + spinal cord) 2,3,4 5-HT- and NA -secreting neurons project upward from their respective nuclei in the brainstem, directly stimulating many areas of the brain Brain areas stimulated include the prefrontal cortex, which is involved in executive functions, and the limbic system which include anatomical structures involved in behaviour, motivation, and emotion, such as the hippocampus, anterior cingulate cortex, hypothalamus, and amygdala 1 REFERENCES: Mega MS, Cummings JL, Salloway S, Malloy P. The limbic system: An anatomic, phylogenetic, and clinical perspective. J Neuropsychiatry Clin Neurosci 1997;9:315-330. Hales RE, Yudofsky SC. Mood disorders. In: Textbook of Clinical Psychiatry . 4th ed. Arlington: American Psychiatric Publishing; 2003:479-486. Coppen A. The biochemistry of affective disorders. Br J Psychaitry 1967;113:1237-64 Schildkraut JJ. The catacholamine hypothesis of affective disorders. A review of supporting evidence. Int J Psychiatry 1967;4:203-17
Core slide For the past 30 years, the leading theory to explain the biological basis of depression has been the monoamine hypothesis. This theory proposes that depression is due to deficiency of one or more monoamine neurotransmitters in the brain. Evidence to date mainly implicates serotonin and noradrenaline. The left diagram illustrates a serotonergic and noradrenergic neurone , in the normal state , releasing serotonin and noradrenaline . All of the cellâs regulatory elements are also functioning properly . In depression, as shown in the diagram on the right, serotonin and noradrenaline are depleted .
Core slide For the past 30 years, the leading theory to explain the biological basis of depression has been the monoamine hypothesis. This theory proposes that depression is due to deficiency of one or more monoamine neurotransmitters in the brain. Evidence to date mainly implicates serotonin and noradrenaline. The left diagram illustrates a serotonergic and noradrenergic neurone , in the normal state , releasing serotonin and noradrenaline . All of the cellâs regulatory elements are also functioning properly . In depression, as shown in the diagram on the right, serotonin and noradrenaline are depleted .
