This document discusses antipsychotic medications, including their history, types, uses, efficacy, and side effects. It covers both typical and atypical antipsychotics, noting that atypicals are now more commonly used due to lower risk of side effects like tardive dyskinesia. Atypicals are effective for positive and negative schizophrenia symptoms as well as mood disorders but can cause metabolic issues. Proper dosing and maintenance treatment are important to prevent relapse.
A compiled Power point presentation on "Antipsychotic drugs" suitable for Undergraduate level medical students and also PG students in the subject of Pharmacology.
Here is an overview of Antipsychotics,starting from basic pathophysiology of Psychosis and Schizophrenia,breifing the Neuropharmacology and lastly introduction of drugs with special reference to side effects and clincal uses.
Typical antipsychotics and dopamine in psychosis Ann Sparks
Overview of TYPICAL/Second Generation Antipsychotics (Neuroleptics, Classic, Conventional, D2 Receptor Antagonists). Includes an historical context, Dopaminergic (Reward) Pathways, Symptoms of Psychosis, Side Effedts of Typical Antipsychotics, and animations (if they "translate!").
A compiled Power point presentation on "Antipsychotic drugs" suitable for Undergraduate level medical students and also PG students in the subject of Pharmacology.
Here is an overview of Antipsychotics,starting from basic pathophysiology of Psychosis and Schizophrenia,breifing the Neuropharmacology and lastly introduction of drugs with special reference to side effects and clincal uses.
Typical antipsychotics and dopamine in psychosis Ann Sparks
Overview of TYPICAL/Second Generation Antipsychotics (Neuroleptics, Classic, Conventional, D2 Receptor Antagonists). Includes an historical context, Dopaminergic (Reward) Pathways, Symptoms of Psychosis, Side Effedts of Typical Antipsychotics, and animations (if they "translate!").
A simple presentation describing medications used in Psychosis.
In this file, you can have a better idea about psychosis, Schizophrenia and their treatment nowadays.
Pharmacology lecture for medical students in English.
A simple presentation describing medications used in Psychosis.
In this file, you can have a better idea about psychosis, Schizophrenia and their treatment nowadays.
Pharmacology lecture for medical students in English.
Update on Risperdal Mass Tort Litigation with Robert MosierLarry Bodine
Hosted by The National Trial Lawyers, the program "Update on Risperdal Mass Tort Litigation" is presented Robert Mosier, a trial lawyer with the law firm of Sanders Phillips Grossman, LLP in Irvine, California.
Risperdal is a very powerful antipsychotic developed by Janssen Pharmaceuticals to treat schizophrenia in adults. However Janssen illegally marketed and sold it to one of the most vulnerable segments of our society – our children – and hid a disfiguring side effect that caused a generation of young boys and men to grow female breasts.
Mr. Mosier discusses cases pending in Philadelphia, Los Angeles, and St. Louis, and rulings by the courts in those jurisdictions.
More than 5,000 cases have been filed across the country, which may be the tip of the spear, because hundreds of thousands of young boys took Risperdal and suffered gynecomastia.
Mr. Mosier’s practice is focused on representing plaintiffs harmed by pharmaceutical and medical device companies. He also maintains an active medical malpractice caseload. He serves as Plaintiff’s Co-Lead Counsel in the Risperdal and Invega Product Liability Cases JCCP 4775. Mr. Mosier is an AV Preeminent Attorney, a member of the Million Dollar Advocates Forum, an Arizona Top Rated Attorney – Top Trial Lawyers in America and National Trial Lawyers – Top 100.
Treatment of epilepsy polytherapy vs monotherapyPramod Krishnan
This presentation reviews the evidence regarding use of early polytherapy in patients with epilepsy with regards to seizure control and adverse effects. The advantages and disadvantages of polytherapy compared to monotherapy is addressed.
TREATMENT RESISTANT DEPRESSION IS A AREA THAT IS NOT EXPLORED MUCH, BUT IT REALLY NEEDS LOT OF ATTENTION AS IT IS ONE OF THE MOST COMMON OBSTACLE IN ACHIEVING COMPLETE REMISSION IN DEPRESSION
Generalized Anxiety DisorderThe term generalized refers to.docxgreg1eden90113
Generalized Anxiety Disorder
The term "generalized" refers to people who suffer from GAD and are afraid of many different things rather than just one or two specific things or sets of circumstances. This can have an emotional and physical impact on the daily living of someone, including fatigue, muscle tension, and increased heart rate. Anxiety can be debilitating, but there are many methods to bring it down to bearable levels. Therefore, symptoms like excessive worrying about various things are characteristic of GAD, making it the most prevalent kind of anxiety disorder. Different therapy approaches for GAD are compared, and the pharmacokinetics and pharmacodynamics of the anxiolytic drugs used to treat the disease will be discussed.
Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs)
Because of their relatively low risk, SSRIs and SNRIs are recommended as first-line treatments for depression. Patients should be informed that they can take these antidepressants from 2 weeks to 6 weeks to start significantly reducing anxiety (Leshem et al., 2021). The first two weeks are when adverse reactions could be potentially at their worst. Increased anxiety or unease at first can make patients less likely to stick with their treatment plan. Some of these symptoms may go away if you start on a lower dose of the antidepressant. However, clinical data suggests that tolerance varies by patient and that a given patient may experience fewer side effects by moving from an SSRI to an SNRI. Several SSRIs and SNRIs are cytochrome P450 enzyme inhibitors, which raises the possibility of drug interactions with other psychopharmacological medications and medical treatment (Leshem et al., 2021). Sudden discontinuation of SSR medications can result in withdrawal symptoms. While unpleasant, these symptoms pale in comparison to those of benzodiazepine withdrawal. These adverse effects may be more familiar with paroxetine than with sertraline or fluoxetine.
Tricyclic Antidepressants (TCAs)
The classic tricyclic antidepressants (TCAs), imipramine and clomipramine, are as effective as second-generation antidepressants in treating anxiety disorders. However, on average, TCAs have more side effects than SSRIs or SNRIs (Schneider, Patterson, & Jimenez, 2019). As a result, these medications should be tried first before using TCAs. The dosage should be gradually increased until it reaches the levels recommended for depression treatment. TCAs should be used with caution in patients at risk of suicide due to the possibility of lethal toxicity following an overdose. All TCAs are rapidly absorbed after oral administration and bind to plasma albumin with a high affinity of 90-95 percent at therapeutic plasma concentrations. Because of their ability to bind to extravascular tissues, they have enormous distribution volumes (10-50 l kg1) (Schneider, Patterson, & Jimenez, 2019). The main mechanisms of inactivation by C.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
16. BLOCKADE OF D2 RECEPTOR IS KEY IN ACTION AND SIDE EFFECTS OF TYPICAL AND ATYPICALS
17. CHEMICAL STRUCTURES A. PHENOTHIAZINES; B. BUTYROPHENONES; C. THIOXANTHENES; D. INDOLE; E. DIBENZAZEPINES; F. BENZISOXAZOLE; G. THIENOBENZODIAZEPINES; H. OTHERS
18. CLOZAPINE IS UNIQUE. IT HAS SIDE EFFECT OF AGRANULOCYTOSIS , BUT HAS NO EPS SIDE EFFECTS AND IS EXCEPTIONALLY EFFECTIVE
21. ABOUT 30% OF PATIENTS WHO DO NOT RESPOND TO STANDARD ANTIPSYCHOTIC WILL RESPOND TO CLOZAPINE IN 12 WEEK TRIAL. IN ANOTHER 15-30%, PATIENTS WHO DO NOT RESOND IN THE FIRST FEW MONTHS WILL RESPOND IN 6-12 MONTHS
42. electroconvulsive therapy (ECT) is effective in treating catatonia and is often helpful, at least to terminate an episode, for patients with drug-resistant schizophrenia.
45. For a patient who has recovered from a first psychotic episode, there is no evidence regarding how long to continue antipsychotic therapy. Probably stopping the drug 2 days after the patient appears much better will lead to a return of psychosis,whereas tapering off medication after 3 months might be toleratedby many patients—perhaps 85%—without relapse rapidly ensuing.
46. schizophrenia is a chronic illness characterized by exacerbations and relative remissions, so maintenance pharmacotherapy is almost always required. At some point, the drug action shifts from being directly antipsychotic to preventing relapse
47. It is clear that antipsychotics are more effective than placebo, but many patients experience a relapse despite adequate drug therapy.
48. Reduced risk of tardive dyskinesia, improved cognitive function, and perhaps greater efficacy in treating negative symptoms have resulted in the atypical antipsychotics being the maintenance treatment of choice for schizophrenia. However, the biggest single drawback to use of atypical agents in maintenance therapy is their greater proclivity for producing significant weight gain compared with standard antipsychotic agents
49. If the patient is expected to be under stress in the next 6–9 months (e.g., completing school, starting a new job, getting divorced), we favor continuing the neuroleptic until the stress point is well past and the patient is generally coping adequately
50. Recent data suggest that in patients with schizophrenia, maintenance therapy, even after the first episode, could alter the course of the illness in a positive manner. Thus, maintenance therapy is beginning to be used earlier in the course of the illness, even after a single episode.
51. At this time, for schizophrenic patients, we favor long-term maintenance at their full antipsychotic dose if possible. Patients who do not tolerate standard doses of classic antipsychotics should be switched to standard doses of atypical antipsychotics. For patients who are unable to tolerate standard doses, we suggest a gradual taper of the antipsychotic dose over 6–9 months to the lowest dose that controls symptoms
52. one of the main reasons antipsychotics do not work is that patients dislike them and refuse to take them, depot antipsychotics have the great advantage that a known amount of drug is administered reliably and that the staff is immediately aware when an injection is missed
53. In more typical, understaffed aftercare programs, depot fluphenazine injections are likely to be much easier to monitor and to be better monitored than pill taking.
54. that low-dose maintenance drug therapy may be necessary for prolonged periods . Again, the newer agents may provide better efficacy and lower risk of tardive dyskinesia. Given the evidence that abrupt stopping of oral antipsychotics may precipitate relapse, more extensive use of depot antipsychotics is indicated for patients with schizophrenia or schizoaffective disorder.
55. these therapies substantially modify the deficits in interpersonal functioning present in patients with chronic schizophrenia, regardless of whether they are taking medication. push themselves or are pushed into rehabilitation, social programs, or work programs that make demands that are beyond their coping abilities and that lead to relapse
58. Atypical antipsychotics already are more commonly used in the treatment of mood disorders than they are in the treatment of schizophrenia. It is likely that the application of these drugs in the treatment of different phases of bipolar disorder will continue to expand
60. When typical antipsychotics are used in treating depression, the medical record should reflect the reasons clearly. When the drug is continued for several months, the risks of dyskinesia must be noted and the need for maintenance neuroleptic use must be specifically justified .
61. The use of atypical antipsychotics in the treatment of depression is also increasing. One growing use of atypicals is in the augmentation of antidepressant response. A number of studies now suggest benefit of adding olanzapine, risperidone, quetiapine, or ziprasidone to a selective serotonin reuptake inhibitor (SSRI) in the treament of resistant depression
63. There are case reports of the utility of olanzapine in the treatment of panic disorder, and we have seen patients who could not tolerate or respond to SSRIs or venlafaxine who have done well with olanzapine monotherapy for their panic symptoms. Still, olanzapine or other atypical antipsychotic agents should be considered only if other strategies fail.
64. antipsychotics can be useful adjunctive agents for the management of agitation, irritable aggression, anxiety, and sleep difficulties in some patients. In addition, PTSD patients seem to benefit from atypical agents in a reduction of reexperiencing symptoms . Because of the sleep and anti-agitation benefits of olanzapine, we often add 5–10 mg of the drug at night to an SSRI or mood stabilizer. Risperidone 1–3 mg in divided doses also seems very helpful for some combat veterans with irritable aggression
65. Anxiety frequently accompanies bipolar disorder. The atypical antipsychotics clearly help mitigate associated symptoms in bipolar patients.
67. Antipsychotics have long been employed in the treatment of patients with borderline and schizotypal personality disorders The paucity of studies is due in part to the difficulties of doing pharmacological trials in patients with personality disorders. Comorbidity with Axis I disorders is common and complicates the selection of patients for studies and the interpretation of study results
68. Schizotypal patients may represent one end of the schizophrenia spectrum and often benefit from antipsychotics. Schizotypal personality in younger patients is often perceived as a prodrome of schizophrenia. The only controlled trial of treating schizoptypal personality patients with an atypical agent, risperidone, reported that a daily dose of 0.5–2 mg was beneficial. Earlier uncontrolled studies with typical antipsychotics also showed benefits
69. antipsychotics have a stabilizing effect on irritability, mood lability, and impulsivity and that they decrease anxiety. They may have a use in the early stages of a more comprehensive treatment program for patients with BPD such as with DBT.
70. At this time, the atypicals have shown more consistent benefit in the the treatment of borderline symptoms than have the typical agents. Given what appears to be a lower long-term risk of some EPS and a broader spectrum of activity for borderline symptoms, the atypicals should generally be used over the typical antipsychotics for the treatment of borderline symptoms
71. Antipsychotics are widely used for agitated organic states such as delirium, Alzheimer's dementia, and mental retardation, with growing evidence that they may be helpful. Studies have called into question the efficacy of the atypical antipsychotics in the treatment of agitation and behavioral dyscontrol associated with dementia.
72. Given the black box warning of increased mortality associated with the atypicals in geriatric patients, it is unclear whether the benefits outweigh the risks The use of antipsychotics in patients with dementia should be assessed on a case-by-case basis.
74. risperidone became the first medication approved for treating the self-aggression and anger associated with pediatric autism
75. Another potential application of atypical antipsychotics is in the treatment of anorexia nervosa. No pharmacotherapy has been demonstrated to help anorexia on a consistent basis at this time. However, early open-label trials, case reports, and at least one controlled trial suggest that olanzapine and quetiapine may help reduce the anxiety and obsessiveness around food and body image while contributing to weight gain
77. Clozapine (Clozaril) has been available in the United States for about 20 years for use with patients who have treatment-resistant schizophrenia or patients who are unable to tolerate the side effects of standard antipsychotics
78. The drug does have problems and dangers, it does not work for everyone, and patients who are helped substantially may still be far from well. Mild cholinergic rebound, faster relapse. Taper as slowly as titrated up.
79. It is also thus far the only antipsychotic drug that causes essentially no pseudoparkinsonism or dystonia and that is, apparently, unlikely to cause tardive dyskinesia.
80. Efficacy Schizophrenia (FDA approved for all) Treatment-resistant schizophrenia (clozapine) Mania (FDA approved for olanzapine, quetiapine, and ziprasidone) Bipolar depression (FDA approved for quetiapine) Depression/anxiety/agitation (efficacy established but not FDA approved for these purposes)
82. Safety in overdose Seizures with clozapine in overdose. Respiratory depression in combination with other CNS depressants. QT interval changes. Lavage and vital sign support
83. Dosage and administration Clozapine: 12.5–25 mg; then increase dosage 25–50 mg per week, as needed and tolerated, to 300–600 mg/day Risperidone: 0.5–1 mg bid to 3 mg bid by end of first week, Olanzapine: 2.5–5 mg hs; increase by 5 mg every week to 20 mg hs Quetiapine: 25 mg bid; increase total daily dose by 50 mg, as needed and tolerated, to 300–600 mg/day Ziprasidone: 20 mg qd or bid; increase by 20–40 mg per week, to a maximum dosage of 80 mg bid Aripiprazole: 15 mg qd; increase up to 30 mg/day after 1 week Full benefits in 4 weeks to 6 months
85. Drug interactions Fluvoxamine (1A2 inhibitor): atypical antipsychotic levels EtOH: sedation and orthostasis Antihypertensives: may orthostasis Carbamazepine: serum levels of olanzapine; clozapine levels; hematological adverse events with clozapine CNS depressants: sedation Ciprofloxacin (Cipro) (potent 1A2 inhibitor): atypical antipsychotic levels
86. clozapine has an odd mix of pharmacological effects: more dopamine1 (D1) than D2 effects, more effect on cortical and limbic dopaminergic systems than on the basal ganglia, and greater serotonergic (5-HT2), histaminic, and -adrenergic blocking activity than other available neuroleptics
87. Patients with chronic schizophrenia who had failed on at least three adequate neuroleptic trials and had not had a remission in 5 years participated in the study. About one-third of the patients improved after taking clozapine for 4 weeks, compared with 2% of patients who improved after taking chlorpromazine
88. Clozapine appears to differ from typical antipsychotics in reducing negative symptoms (e.g., withdrawal, lack of motivation). Clozapine clearly reduces them, as do all the newer atypical agents. In addition, clozapine may also affect other dimensions of schizophrenia, such as suicidality
89. Clozapine may be better than any of the atypicals in reducing impulsive aggression, and it this property that may account for its reported ability to reduce self-aggression, self-mutilation, and suicide attempts. Although the side-effect profile of clozapine will typically prevent its use as a first- or second-line agent, we have seen a number of cases in which clozapine was used effectively to reduce self-destructive behavior in schizophrenia, bipolar disorder, and even BPD patients
90. Because of its tendency to cause serious agranulocytosis—affecting as many as 1.2% of all treated patients in the United States—clozapine is marketed under a unique system: all patients who are to begin taking clozapine must be cleared through a national registry (one of five currently in existence), and the physician and the pharmacy are responsible for obtaining weekly white blood cell counts (WBCs) for all these patients, essentially forever. Weekly supplies of clozapine are dispensed at the time the blood is drawn
91. The agranulocytosis associated with clozapine use is believed to be an autoimmune reaction, not a direct toxic effect on the bone marrow. It is not dose related. Most cases occur in the second through fourth months of treatment, but some reactions have occurred as late as 18 months after the drug was begun. Patients developing agranulocytosis once will rapidly develop it again if the drug is restarted
92. Clozapine is available generically in 12.5-mg, 25-mg, 50-mg, 100-mg, and 200-mg tablets, and in 25-mg and 100-mg scored disintegrating tablets. The starting dosage is 25 mg at bedtime, and the manufacturer recommends dosing bid, but many patients end up taking the whole dose at bedtime. The dosage should be increased slowly and cautiously from 25 mg/day to 200 mg/day over the first 2–3 weeks, then stabilized at that dosage for a few weeks, with further increases as tolerated. Most patients respond well to dosages between 300 and 500 mg/day. If clear improvement has not occurred, the dosage can be gradually increased to 900 mg/day
93. drug-related grand mal seizures occur quite frequently (in about 15% of patients) at dosages over 550 mg/day, anticonvulsants should probably be added. Phenytoin or valproate, in standard anticonvulsant doses, are used for this purpose
94. Sedation is one major side effect limiting dosage increases.
95. Drug-induced fevers of around 100˚F can occur early in treatment but pass and are not serious
96. Although the manufacturer has strongly urged that other antipsychotics be withdrawn from patients before clozapine is begun, this advice is hard to follow with many psychotic patients.
97. We have seen several cases of neuroleptic malignant syndrome (NMS) associated with clozapine use, particularly in patients on concurrent lithium
98. The course of improvement with clozapine treatment is somewhat unpredictable. Patients who clearly show a substantial decrease in psychotic symptoms may do so in the first few weeks of treatment or as late as 3–6 months or more later. Some patients—a third or more in our experience—show marked improvement, although most are not totally free of psychotic residua
99. Psychotic and nonpsychotic patients with treatment-resistant mania also usually respond. Patients who take clozapine for 1 or more years may show gradual, continuing improvement. Even minimally improved psychotic patients may be less impulsively angry, violent, or argumentative and may show a gratifying absence of distressing akathisia, parkinsonism, and akinesia .
100. Long-term side effects of maintenance clozapine therapy are not known, although in the United States, a handful of patients have been taking the drug continuously for over 20 years without known adverse effects (including tardive dyskinesia). With long-term treatment with clozapine, the majority of patients gain weight
101. All the atypical antipsychotics, especially clozapine, olanzapine, and quetiapine, have been thought to be associated with an increased risk of of hyperglycemia and diabetes, and this is now reflected as a warning in the package inserts of all atypical antipsychotics
102. If the patient has gained more than 5% of body weight or has a BMI over 30, we may check glucose and lipid levels as frequently as every month until we are convinced that the patient is medically stable. A finger stick is probably more useful than a hemoglobin A1c (HbA1c), unless the patient is already diabetic. The HbA1c is somewhat too global and blunt an assessment to tell us what is happening on a day-to-day basis. A fasting glucose or a finger stick is probably the most useful assessment to obtain in monitoring glucose levels
103. Physicians sometimes stop clozapine because patients have a transiently low WBC (3,000–3,999 cells/mm3); such patients never actually had agranulocytosis. These patients often respond to a second trial of clozapine without ever developing true agranulocytosis.
104. The combined cost of the required weekly WBCs and the drug is relatively high. However, most insurance carriers may cover all or a portion of the costs; the fiscal cost-benefit ratio for patients in public or private institutions has been determined, and the results favor the use of clozapine. For example, under Medicare Part D, clozapine is covered by most Prescription Drug Plans (PDPs) under a tiered system, depending on the plan. Now that clozapine is available generically, virtually all county mental health programs are purchasing the generic formulation at great savings over the name brand
106. Risperidone (Risperdal) was the next atypical antipsychotic agent introduced in the United States after clozapine for general prescription use. The drug exerts relatively more D2 than D1 antagonism. It also has antagonist effects at 5-HT2 and possibly 5-HT1 receptors
107. The 6-mg (3 mg bid) dosage is at least as effective as 20 mg of haloperidol.
108. At these lower doses, it is unclear whether risperidone maintains a significant edge over haloperidol regarding the rates of EPS
109. Risperidone is indicated in the treatment of schizophrenia, schizoaffective disorder, acute mania, and mixed states. Risperidone was also approved both as a monotherapy and as an adjunctive agent in the treatment of acute mania and is approved in the treatment of irritability and mixed states in patients with autism. The utility of risperidone as a maintenance treatment or a treatment for bipolar depression is as yet unclear. As reported earlier in this chapter, risperidone also has shown benefits in the augmentation treatment of unipolar depression
110. Risperidone seemed the ideal drug as a first-line treatment for psychotic patients until worrisome adverse effects began to be noticed: EPS,
111. orthostatic hypotension, agitation, oversedation, and so forth. Orthostasis has been particularly problematic in some patients and occasionally results in syncope and falls
113. Staying low in dose and going slow with everybody, but even lower and slower with older patients or patients taking multiple medications, seems wise
114. In elderly patients, starting risperidone at a dosage of 0.5 mg qd or bid and slowly titrating the drug upward appears prudent, and we tend to keep the dosage below 1–2 mg/day for the first 2 weeks in an attempt to limit side effects.
115. Risperidone may turn out, in the long run—if used wisely and well—to be the ideal first-line antipsychotic, to lead to better control of both negative and positive symptoms, and to cause less tardive dyskinesia and NMS. However, compared with other atypicals, risperidone causes more EPS particularly when the dosage is pushed much beyond 6 mg/day. The cumulative risk of tardive dyskinesia with risperidone treatment for 1 year is around 0.5%–1% in younger patients and perhaps as high 2.6 % in older patients.
116. A long-acting depot formulation, Risperdal Consta, is available for maintenance therapy. Typical dosages range from 25 to 50 mg every 2 weeks.
117. Weight gain while taking risperidone is generally much less of a problem than it is with clozapine, olanzapine, or quetiapine. Our sense is that weight gain with risperidone is probably more comparable to that seen with aripiprazole and ziprasidone
118. In changing patients from a typical antipsychotic (or clozapine), it is unwise to discontinue the older antipsychotic, wait 2 weeks, and then start risperidone. Phasing the new drug in slowly while phasing the older drug out should lessen the chance of relapse
119. A metabolite of risperdone, paliperidone (in extended-release tablets), has recently been approved by the FDA for the treatment of schizophrenia. It may have some advantages over risperidone in side effects, but these remain to be established. A sustained-release form and a depot form of paliperidone are under development
121. Like other atypical antipsychotics, it has a high binding ratio of 5-HT2 to D2 receptors. The receptor-binding affinities of olanzapine appear to lie somewhere between the very broad receptor effects of clozapine and the more narrow receptor binding of risperidone.
122. Like clozapine, olanzapine is an antagonist of dopamine receptors (D1–D4) and the 5-HT2 receptor. In addition, it is antihistaminic, is anticholinergic, and blocks 1-adrenergic receptors.
123. Olanzapine is metabolized primarily via the cytochrome P450 enzymes 1A2 and, to a lesser extent, 2D6
124. Olanzapine appears to be at least as effective as haloperidol in the short-term treatment of schizophrenia. It may be better than haloperidol in improving negative symptoms, concurrent depression and suicidality, and cognition. In addition, in premarketing studies, olanzapine 10–20 mg/day was associated with significant improvement in positive symptoms, including delusions, hallucinations, and thought disorder.
125. Olanzapine is now approved for the treatment of a variety of disorders other than schizophrenia. Olanzapine was the first atypical antipsychotic approved for the treatment of acute mania. It probably works faster and at least as effectively as does lithium or valproate. In addition, olanzapine became the third drug, after lithium and lamotrigine, to show benefit in the prevention of mania and depression in bipolar I patients. Olanzapine, when combined with fluoxetine, became the first drug approved for the treatment of bipolar depression. Olanzapine by intramuscular injection has been approved for the acute treatment of agitation in patients with schizophrenia and bipolar disorder. As previously reported, olanzapine also appears to have a role in treating psychotic depression, and perhaps as an augmenting agent in treating unipolar depression
126. It remains unclear whether olanzapine is as useful as clozapine in the treatment of refractory schizophrenia, even though comparison studies have generally found the drugs to be equally effective in this context . Olanzapine is a fairly "dirty" drug, in that it affects multiple neurotransmitter systems, but it is not quite as "dirty" as clozapine. It is this "dirtiness" that contributes to clozapine's toxicity but that may also be important in theefficacy of the drug in more refractory cases.
127. Head-to-head trials of olanzapine and risperidone in refractory depression also suggest that the drugs are probably equally effective but differ in side-effect profiles. Olanzapine is associated with more weight gain and sedation, whereas risperidone is more likely to increase prolactin levels and produce EPS
128. Head-to-head trials of olanzapine and risperidone in refractory depression also suggest that the drugs are probably equally effective but differ in side-effect profiles. Olanzapine is associated with more weight gain and sedation, whereas risperidone is more likely to increase prolactin levels and produce EPS.
129. At least 10% of patients will develop akathisia in an acute 6-week trial at dosages of 10 to 15 mg/day. We have found that propranolol 10 mg bid or tid can help with this problem. However, some patients have a significant worsening of postural hypotension with even small additions of -blockers, so caution is advised
130. Dystonic reactions and dyskinesias appear to be quite uncommon with olanzapine at usual dosages. However, patients do tend to report more severe parkinsonian symptoms with increasing dosages of the drug, including feeling stiffer and more slowed down. About 20% of patients will report Parkinson's-type symptoms at dosages above 10 mg/day. Anticholinergic agents clearly help if parkinsonism develops.
131. NMS appears to be uncommon but not unheard of with olanzapine use
132. Anticholinergic side effects such as constipation and dry mouth occur in 5%–10% of patients taking olanzapine at therapeutic dosages. Like risperidone and clozapine, olanzapine produces -adrenergic blockade, resulting in a dose-related increase in orthostasis and dizziness. We suggest monitoring orthostatic blood pressures, particularly with older patients and those with a history of postural hypotension
133. The most problematic side effects with long-term, maintenance use of olanzapine are weight gain and sedation. At least 29% of patients will gain more than 7% of their body weight in a 6-week trial, and 5.4 kg, or about 12 lb, is the average weight gain with long-term use .However, we have seen some patients gain 50 lb or more in a year. This weight gain is terribly distressing for many patients. Large weight gains have been thought to be associated with insulin resistance and dyslipidemias, although the former has not been clearly demonstrated. As with other atypicals, patients taking olanzapine should be screened and monitored for metabolic symptoms
134. The weight gain associated with olanzapine appears to be, at least in part, from an increased appetite, and we warn patients that olanzapine can result in their desire to eat more. Most of the weight gain that occurs with olanzapine appears to occur in the first 6 months, with gain then appearing to plateau for up to 3 years.
135. Olanzapine is very sedating for many patients and should be taken at bedtime if possible. About 40% of patients will report daytime somnolence at a dosage of 15 mg/day. Taking the olanzapine on an empty stomach about an hour before bedtime may increase the nighttime sedation and reduce the daytime somnolence. The use of modafinil in doses of 100–200 mg in the morning may help mitigate the somnolence.
136. There are no reported cases of agranulocytosis, and no blood count monitoring is recommended.
138. An intramuscular formulation of olanzapine is available for acute management at doses of 2.5–10 mg per day. In addition, a depot form of olanzapine is under development