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Major Depression & Bipolar Disorder Janey, Kevin, & Brittany Ch 15 Major Depression • MDD vs Bipolar • Depression is an affective disorder characterized by loss of interest or pleasure • Bipolar disorder (manic-depressive disorder) is characterized by recurrent episodes of mania and depression Ch 15: Major Depression • Depression and the Brain – Deficiencies in the brain catecholamines(norepinephrine and dopamine) are thought to underlie major depressive episodes while acute drug-induced increases correlate with relief from depression • inconsistencies in the pattern have also been found Ch 15: Major Depression • Effects of Antidepressants Antidepressasnt drugs may increase the sensitivity of postsynaptic catecholamine and serotonin receptors and may decrease the sensitivity of presynaptic receptor sites. The net effect is the reregulation of an abnormal receptorneurotransmitter relationship; speeding up the patient’s natural recovery process from the depressive episode by normalizing neurotransmitter efficacy. Stress and other insults to the brain decrease the expression of BDNF, which leads to atrophy of vulnerable neurons in the hippocampus and cerebral cortex; Antidepressant drugs must work to reverse the atrophy Ch 15: Major Depression • Seven Classes of Antidepressants 1. Tricyclic Antidepressants 2. Atypical Antidepressants 3. SSRI’s 4. Dual-Action Antidepressants 5. MAOI’s 6. COMT Inhibitors 7 SNRI’s Ch 15: Major Depression • Imipramine vs Fluxetine – Imipramine is a tricyclic antidepressant that blocks the presynaptic transporter of protein receptor for either dopamine or norepinephrine – Fluoxetine (Prozac) was the first SSRI-type antidepressant available in the U.S. It blocks the function of the presynaptic transporter for serotonin reuptake, but does not appear to block reuptake of other neurotransmitter to any significant degree Ch 15: Major Depression • Tricyclics and Overdosing – The patient that overdoses on tricyclics exhibits excitement, delirium, and convulsions, followed by respiratory depression and coma, which can persist for several days. TCA’s are also cardiotoxic and potentially fatal. Who’s at risk? – Children, adolescents and the severely depressed (suicidal) are particularly at risk Ch 15: Major Depression • Side effects of SSRIs – Anxiety, agitation, and insomnia • Serotonin Syndrome? – Occurs when SSRI’s are taken in high doses or combined with other drugs. Increased central accumulation of serotonin leads to an exaggerated response, characterized by alterations in cognition (disorientation, confusion, hypomania), behavior (agitation, restlessness), autonomic nervous system functions (fever, shivering, chills, sweating, diarrhea, hypertension, tachycardia), and neuromuscular activity (ataxia, increased reflexes, myoclonus) Ch 15: Major Depression • Serotonin Withdrawal Syndrome – characterized by disequilibrium (dizziness, vertigo, ataxia); gastrointestinal symptoms (nausea, vomiting, diarrhea); flu-like symptoms (fatigue, lethargy, myalgia, chills); sensory disturbances (paresthesia, sensation of electric shocks); sleep disturbances (insomnia, vivid dreams); – psychological symptoms include anxiety, agitation, crying spells and irritability – sexual dysfunction occurs in about 60% of patients Ch 15: Major Depression • Antidepressants and Children – TCA’s are considered no more effective than placebo for MDD – SSRI’s have efficacy in treatment for 13 different conditions including depression and OCD • Antidepressants and Anxiety Disorders – TCA’s, MAOI’s, SSRI’s and venlafaxine XR (effexor) are all in use for anxiety disorders. The newer antidepressant-anxiolytic drugs are equally or more efficacious than benzodiazepine-type. They are less prone to compulsive abuse but impair learning, memory and concentration to a lesser degree than do the benzodiazepines Ch 15: Major Depression • What is DHEA? – DHEA is a major glucocorticoid hormone secreted by the adrenal glands – It has been promoted (with minimal evidence) to prevent heart disease, cancer, diabetes, obesity, dementia, aging, multiple sclerosis, and lupus; it increases feelings of physical and psychological well being. DHEA, but not placebo, exerted a robust effect on mood, improving low energy, anhedonia, lack of motivation, emotional flattening (numbness), sadness, excessive worry and inability to cope. – Potential side effects include acne, male-pattern baldness, hirsutism, voice changes. Also may cause breast or prostate cancer and liver damage