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Drugs for Treating Psychiatric Disorders Chapter 13 What are Psychotropic Medications? Medications are used to treat the symptoms of mental disorders such as schizophrenia, depression, bipolar disorder (sometimes called manic-depressive illness), anxiety disorders, and attention deficit-hyperactivity disorder (ADHD). Side Effects to Psychotropic Drugs? Some people get side effects from medications and other people don't Factors that can affect how medications work in people include: Type of mental disorder, such as depression, anxiety, bipolar disorder, and schizophrenia Age, sex, and body size Physical illnesses Habits like smoking and drinking Liver and kidney function Genetics Other medications and herbal/vitamin supplements Diet Whether medications are taken as prescribed. Depression Symptoms Most symptoms, felt most days over 2 weeks • Depressed mood most of the day, • Markedly diminished interest or pleasure • Significant weight loss when not dieting or weight gain • Insomnia or hypersomnia • Psychomotor agitation or retardation • Fatigue or loss of energy • Feelings of worthlessness or guilt • Diminished ability to think or concentrate, or indecisiveness • Recurrent thoughts of death Depression Most common drugs used: • Tricyclic antidepressants (TCAs) used mostly in the past though no other group of antidepressants was been demonstrated as more effective or fast working) – Elavil, Tofranil, Pamelor • Selective serotonin reuptake inhibitors (SSRIs) – Celexa, Prozac, Lexapro, Paxil, Zoloft • Serotonin–norepinephrine reuptake inhibitors (SNRIs) – Effexor, Pristiq, Cymbalta, Dalcipran, Meridia • Monoamine oxidase inhibitors MAOIs (used rarely) – Apresoline, Harmalol, Selegiline, Moclobemide TCAs Pharmacokinetics Absorption • Orally (once a day at bedtime to minimize unwanted side effects like persistent sedation) Distribution • 4 days of clinical effect and readily crosses the placental barrier Metabolism • Rapidly and almost completely metabolized by enzymes located in the liver. Elimination • Urine TCAs Related Neurotransmitters Therapeutic effects comes from blocking reuptake of dopamine, serotonin, and norepinephrine Blockade of ACH receptors results in dry mouth, confusion, memory impairments, and blurred vision Blockage of histamine receptors results in drowsiness and sedation TCAs Effects Elevated mood Increased physical activity Improved appetite Improved sleep patterns Reduced morbid preoccupation Clinically effective in the long-term therapy of dysthymia Dry mouth Confusion Memory impairments Blurred vision Sedation* Cardiac depression Cardiac arrhythmias SSRIs Related Neurotransmitters Blocks the re-uptake of serotonin *Each drug has a different half life SSRIs Effects Elevated mood Increased physical activity Improved appetite Improved sleep patterns Reduced morbid preoccupation Clinically effective in the long-term therapy of dysthymia Sexual dysfunction > 60% Anxiety Agitation Insomnia Rarely suicide SSRIs Caution! Suicide Serotonin syndrome (most likely to occur when SSRIs are combined with each other, other antidepressants, or valerian root) - Alterations in cognition, autonomic nervous system, and neuromuscular activity which could be life threatening. Serotonin Withdrawal Syndrome (occurs in perhaps 60% of SSRI-treated patients following drug removal) - Disequilibrium, gastrointestinal symptoms, sensory disturbances (sensation of electric shocks), sleep disturbances SNRIs Related Neurotransmitters Blocks the reuptake of serotonin Blocks the reuptake of norepinephrine SNRIs Effects Elevated mood Increased physical activity Improved appetite Improved sleep patterns Reduced morbid preoccupation Clinically effective in the long-term therapy of dysthymia Dry mouth Dizziness nausea Blurred vision Sedation* SNRIs Caution! Suicide Serotonin syndrome (most likely to occur when SSRIs are combined with each other, other antidepressants, or valerian root) - Alterations in cognition, autonomic nervous system, and neuromuscular activity which could be life threatening. Serotonin Withdrawal Syndrome (occurs in perhaps 60% of SSRI-treated patients following drug removal) - Disequilibrium, gastrointestinal symptoms, sensory disturbances (sensation of electric shocks), sleep disturbances MAOIs Related Neurotransmitters Breaks down norepinephrine and serotonin permanently –which means it could be weeks before new neurotransmitters are manufactured. MAOIs Effects Elevated mood Increased physical activity Improved appetite Improved sleep patterns Reduced morbid preoccupation Clinically effective in the long-term therapy of dysthymia Potential fatal blood pressure increases when mixed with common foods MAOIs Caution! Death when mixed with common foods like cheese, wine, beer, soy, coffee, chocolate Serotonin syndrome (most likely to occur when MAOIs are combined with each other, other antidepressants, or valerian root) - Alterations in cognition, autonomic nervous system, and neuromuscular activity which could be life threatening. Wellbutrin (Bupropion) works on the neurotransmitter dopamine, is unique in that it does not fit into any specific drug type. Herbal Remedies for Depression? NIH conducted a clinical trial to determine the effectiveness of treating adults who have major depression with St. Johns wort. The single-blind study included 340 people diagnosed with major depression. 1/3 took the herbal medicine, 1/3 took an SSRI, and 1/3 took placebo. The study found that St. John's wort was no more effective than the placebo in treating major depression Bipolar Disorder Depressive Symptoms 5 or more, in same 2 week period • Depressed mood most of the day, • Markedly diminished interest of pleasure • Significant weight loss when not dieting or weight gain • Insomnia or hypersomnia • Psychomotor agitation or retardation • Fatigue or loss of energy • Feelings of worthlessness or guilt • Diminished ability to think or concentrate, or indecisiveness • Recurrent thoughts of death Bipolar Disorder Mania Symptoms 3 or more, lasting at least 1 week • inflated self-esteem or grandiosity • decreased need for sleep • more talkative than usual or pressure to keep talking • flight of ideas or subjective experience that thoughts are racing • distractibility increase in goal-directed activity or psychomotor agitation • excessive involvement in pleasurable activities that have a high potential for painful consequences Bipolar Disorder 4% LPR Laryngopha -ryngealreflux > 55% have a history of substance abuse 1 in 4 or 5 commits suicide Must rule out mania caused by antidepressants, caffeine, herbals, stimulants, corticosteroids, cough and cold preparation, diet aids, and hyperthyroid Bipolar Disorder Most common drugs used: • Lithium • 28% of patients discontinue the drug • 38% experience recurrences on the drug • Only 23% don’t have reoccurring episodes • Valproic Acid • Antipsychotics Lithium –a salt Pharmacokinetics Absorption • Orally (once daily due to long half life) Distribution Metabolism • Peak blood levels reach within 3 hours; crosses blood-brain barrier incompletely • Excreted unchanged by kidneys Elimination • Urine and skin Lithium Effects Less mania (though not less time to recurrence compared to placebo) Reduction in suicidal behaviors Nausea, vomiting, diarrhea, abdominal pain tremor, lethargy, impaired concentration, slurred speech, ataxia, muscle weakness Memory loss Weight gain (depressed thyroid) Hallucinations Muscle rigidity, coma, renal failure, cardiac arrhythmias, and death Lithium Caution! Illness course is believed to be worse after stopping lithium than having never received the drug (including super high suicidal behaviors and completions). Low compliance due to side effects, high likelihood of relapse, and missing the “high” High rate of interactions with other drugs About 40% are either resistant to lithium or develop side effects that limit its effectiveness Valproic Acid –antiepileptic drug Pharmacokinetics Absorption • Orally and intravenously for acute mania Distribution • 90% bound to proteins in blood, 10% may make it to the brain (this Metabolism Elimination % rises shockingly if too much is administered) • 95% broken down by liver; with metabolites that contribute to side effects. Differences between peak and trough levels can be extreme • Urine Valproic Acid Effects Less mania (though not less time to recurrence compared to placebo) Reduction in suicidal behaviors GI upset Sedation Lethargy Hand tremor Alopecia (loss of hair) Metabolic changes in liver Decreased cognitive function Obesity (rarer side effects) Fertility problems in women and masculinization Valproic Acid Caution! Causes excess ammonia in the blood (hyperammonemia) which can lead to brain damage Overdose = tremor, stupor, respiratory depression, coma, metabolic acidosis and death Antidepressants used in treatment of bipolar disorder • Fluoxetine (Prozac), paroxetine (Paxil), or sertraline (Zoloft) are sometimes given to people with bipolar disorder • CAUTION: should not take an antidepressant on its own. Doing so can cause the person to rapidly switch from depression to mania Atypical Antipsychotics Related Neurotransmitters Serotonin antagonism Atypical Antipsychotics Effects Less mania (depending on drug used) More mania (depending on drug used) Sedation (in some drugs) Increased motor activity Agitation Weight gain Extrapyramidal effects Akathesia (sensation of inner restlessness) Tardive dyskinesia (purposeless movements) Schizophrenia Symptoms 2 or more for a sig. portion of time during 1-mo. period • delusions • hallucinations • disorganized speech (e.g., frequent derailment or incoherence, echolalia) • grossly disorganized or catatonic behavior • negative symptoms (i.e. affective flattening, mental confusion, or lack of initiation/motivation) Schizophrenia 1% LPR 10-15% commit suicide Schizophrenia and the Brain Animation Schizophrenia Most common drugs used: • Typical Antipsychotics (also called neuroleptics) - Clozapine, Thorazine, Haldol, • Atypical antipsychotics – Risperdal, Abilify, Seroquel Typical Antipsychotics Related Neurotransmitters Dopamine receptor blockage Typical Antipsychotics Effects Less positive symptoms of schizophrenia Worse negative symptomatology of schizophrenia Sedation Extrapyramidal effects Akathesia (sensation of inner restlessness) Tardive dyskinesia (purposeless movements) Atypical Antipsychotics Related Neurotransmitters Serotonin antagonism Atypical Antipsychotics Effects Less positive symptoms of schizophrenia Sedation (in some drugs) Increased motor activity Agitation Weight gain Extrapyramidal effects Akathesia (sensation of inner restlessness) Tardive dyskinesia (purposeless movements) Medications for Anxiety Disorders Anxiety disorders include: Obsessive compulsive disorder (OCD) Post-traumatic stress disorder (PTSD) Generalized anxiety disorder (GAD) Panic disorder Social phobia Fear of open and closed spaces (agoraphobia) Antidepressants, anti-anxiety medications, and beta-blockers are the most common medications used for anxiety disorders. Generalized Anxiety Disorder Symptoms 3 or more, felt most days over 6mos • Feeling wound-up, tense, or restless • Easily becoming fatigued or worn-out • Concentration problems • Irritability • Significant tension in muscles • Difficulty with sleep Generalized Anxiety Disorder Most common drugs used: • Buspirone (Buspar) • Benzodiazepines ► • SSRIs – Celexa, Prozac, Lexapro, Paxil, Zoloft • SNRIs – Effexor, Pristiq, Cymbalta, Dalcipran, Meridia Buspar (buspirone) Related neurotransmitters unknown (possible serotonin receptor agonist; possible dopamine antagonist) Buspar (buspirone) Effects Anxiety remission with less withdrawal symptoms than benzos dizziness Headache Lightheadedness nausea Excitement Sweating/clamminess Attention Deficient Hyperactivity Disorder Inattention Symptoms 6 or more, in more than one situation + • • • • • • • • • Often does not give close attention to details or makes careless mistakes in schoolwork, work, or other activities. Often has trouble keeping attention on tasks or play activities. Often does not seem to listen when spoken to directly. Often does not follow instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions). Often has trouble organizing activities. Often avoids, dislikes, or doesn't want to do things that take a lot of mental effort for a long period of time (such as schoolwork or homework). Often loses things needed for tasks and activities (e.g. toys, school assignments, pencils, books, or tools). Is often easily distracted. Is often forgetful in daily activities. Attention Deficient Hyperactivity Disorder Hyperactivity Symptoms Maladaptive in more than one situation • • • • • • Often fidgets with hands or feet or squirms in seat. Often gets up from seat when remaining in seat is expected. Often runs about or climbs when and where it is not appropriate (adolescents or adults may feel very restless). Often has trouble playing or enjoying leisure activities quietly. Is often "on the go" or often acts as if "driven by a motor". Often talks excessively. Impulsivity Symptoms Maladaptive in more than one situation • Often blurts out answers before questions have been finished. • Often has trouble waiting one's turn. • Often interrupts or intrudes on others Attention Deficient Hyperactivity Disorder ADHD animation http://www.healthcentral.com/adhd/video-39189-47.html Attention Deficient Hyperactivity Disorder Most common drugs used: • Ritalin► • Adderal ► Less common drugs used • Methamphetamine ► Special Needs Groups • Psychiatric medications are taken by all types of people, but some groups have special needs, including: – Children and adolescents – Older adults – Women who are pregnant or may become pregnant. Children • Great care needs to be taken in prescribing psychotropic drugs to children • FDA indicated that Prozac should never be used in children because of brain damage issues • Brain is still developing and impacted more negatively than in adults Older Adults • Often have more medical problems than other groups and tend to take more medications than younger people, including prescribed, over-the-counter, and herbal medications. • Higher risk for experiencing bad drug interactions, missing doses, or overdosing. • More sensitive to medications. • More likely to experience paradoxical effects Women – pregnant or planning Research is inconsistent in determining whether antidepressants are safe during pregnancy Some research suggests the use of SSRIs during pregnancy is associated with miscarriage or birth defects, but other studies do not support this Fetuses exposed to SSRIs during the third trimester may be born with "withdrawal" symptoms such as breathing problems, jitteriness, irritability, trouble feeding, or hypoglycemia (low blood sugar). Some medications should not be taken during pregnancy. Benzodiazepines may cause birth defects or other infant problems, especially if taken during the first trimester. Mood stabilizers are known to cause birth defects. Benzodiazepines and lithium have been shown to cause "floppy baby syndrome," which is when a baby is drowsy and limp, and cannot breathe or feed well.