The document discusses the pharmacotherapy of schizophrenia. It begins by outlining the objectives of recognizing symptoms, explaining pathophysiology, identifying treatment goals, and comparing antipsychotic medications. It then covers the introduction, etiology, types, pathophysiology, signs and symptoms, and management of schizophrenia including current practices. Management involves psychosocial interventions, medications, and ECT. Treatment is divided into acute, stabilization, and maintenance phases. The document provides recommendations for antipsychotic selection and monitoring side effects. It acknowledges controversies around first-generation versus second-generation antipsychotics and long-acting injections.
Discussion 1
Segura Herrera, Rafael E
YesterdaySep 26 at 10:40pm
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C.Z. Case Discussion
C.Z. presents with delusion, hallucination, trouble focusing, thought disorders, and speech difficulties. These symptoms suggest C.Z. has schizophrenia, as defined by the American Psychological Association (APA; 2020). Also, DSM-V include 2 or more criteria present for a significant portion of time during 1 month period, C.Z. has delusion, hallucination This paper describes schizophrenia’s etiology, course, associated abnormalities, and management.
Etiology
Schizophrenia’s etiology includes several possible causes. Potential causes include heredity, stressful events, alcohol, and substances use, especially amphetamine and cannabis, and perinatal, neuroanatomic, and neurodevelopmental factors (Rosenthal & Burchum, 2021; Hany et al., 2022). Social isolation, childhood trauma, family history, and urbanization also heighten risk (Hany et al., 2022). However, the specific cause is unknown.
Course
The course of schizophrenia is varied. Some patients may show subtle, gradual changes before schizophrenia symptoms manifest (Rosenthal & Burchum, 2021). Once the illness develops, acute episodes feature delusions and hallucinations symptoms (Rosenthal & Burchum, 2021). Patients may have less vivid residual symptoms after the acute episode, including suspiciousness, diminished judgment, reduced self-care capacity, and poor anxiety management (Rosenthal & Burchum, 2021). The condition’s long-term course features episodic acute exacerbations with partial remission intervals with progressive decline in social functioning and mental status becoming evident with time (Rosenthal & Burchum, 2021). Others may have continuous symptoms. Appropriate treatment can prevent long-term deterioration and reduce acute relapse risk.
Structural/Functional Abnormalities
Notably, schizophrenia is linked to structural and functional abnormalities. Imaging tests have shown structural abnormalities, including disrupted white matter integrity and reduced gray matter volume in parietal and temporal regions (Zhao et al., 2018). Functional abnormalities are present since schizophrenia is linked to a dysregulation of dopaminergic signaling and increased striatal activity (Zhao et al., 2018). Other functional abnormalities include abnormal neural activity and emotional and cognitive dysfunction (Zhao et al., 2018). Notably, the abnormalities occur over the disease’s course, with Zhao et al. (2018) observing abnormalities before symptoms emerge and becoming more evident with the onset of the illness.
Treatment
Pharmacotherapy is recommended for schizophrenia for symptom management to enhance and maintain recovery. APA (2020) guidelines recommend antipsychotics for patients with schizophrenia (Keepers et al., 2020). Medications for this disorder could be classified typical and atypicals, the first one also by binding affinity with D2 receptor: low, medium, and high. ...
Discussion 1
Segura Herrera, Rafael E
YesterdaySep 26 at 10:40pm
Manage Discussion Entry
C.Z. Case Discussion
C.Z. presents with delusion, hallucination, trouble focusing, thought disorders, and speech difficulties. These symptoms suggest C.Z. has schizophrenia, as defined by the American Psychological Association (APA; 2020). Also, DSM-V include 2 or more criteria present for a significant portion of time during 1 month period, C.Z. has delusion, hallucination This paper describes schizophrenia’s etiology, course, associated abnormalities, and management.
Etiology
Schizophrenia’s etiology includes several possible causes. Potential causes include heredity, stressful events, alcohol, and substances use, especially amphetamine and cannabis, and perinatal, neuroanatomic, and neurodevelopmental factors (Rosenthal & Burchum, 2021; Hany et al., 2022). Social isolation, childhood trauma, family history, and urbanization also heighten risk (Hany et al., 2022). However, the specific cause is unknown.
Course
The course of schizophrenia is varied. Some patients may show subtle, gradual changes before schizophrenia symptoms manifest (Rosenthal & Burchum, 2021). Once the illness develops, acute episodes feature delusions and hallucinations symptoms (Rosenthal & Burchum, 2021). Patients may have less vivid residual symptoms after the acute episode, including suspiciousness, diminished judgment, reduced self-care capacity, and poor anxiety management (Rosenthal & Burchum, 2021). The condition’s long-term course features episodic acute exacerbations with partial remission intervals with progressive decline in social functioning and mental status becoming evident with time (Rosenthal & Burchum, 2021). Others may have continuous symptoms. Appropriate treatment can prevent long-term deterioration and reduce acute relapse risk.
Structural/Functional Abnormalities
Notably, schizophrenia is linked to structural and functional abnormalities. Imaging tests have shown structural abnormalities, including disrupted white matter integrity and reduced gray matter volume in parietal and temporal regions (Zhao et al., 2018). Functional abnormalities are present since schizophrenia is linked to a dysregulation of dopaminergic signaling and increased striatal activity (Zhao et al., 2018). Other functional abnormalities include abnormal neural activity and emotional and cognitive dysfunction (Zhao et al., 2018). Notably, the abnormalities occur over the disease’s course, with Zhao et al. (2018) observing abnormalities before symptoms emerge and becoming more evident with the onset of the illness.
Treatment
Pharmacotherapy is recommended for schizophrenia for symptom management to enhance and maintain recovery. APA (2020) guidelines recommend antipsychotics for patients with schizophrenia (Keepers et al., 2020). Medications for this disorder could be classified typical and atypicals, the first one also by binding affinity with D2 receptor: low, medium, and high. ...
Fibromyalgia is characterized by chronic widespread pain, increased tenderness at specific sites known as “tender points,” unrefreshing sleep, fatigue and cognitive dysfunction not attributable to other disease states.
Fibromyalgia affects 2–4% of the general population and of those affected, 80–90% are female. In general, symptom onset occurs between the ages of 30 and 60.
While the etiology of fibromyalgia is not entirely clear, associations with trauma, adverse life events, impaired mood (e.g., depression), anxiety, irritable bowel syndrome, irritable bladder syndrome, cold intolerance, paresthesias and other medical condition have been described. Consequently, a patient tailored approach to treatment is ideal to address both symptoms of fibromyalgia and any associated conditions.
Medication-induced movement disorder (Extra-Pyramidal Side Effects, EPSE) occurs due to treatment with antipsychotic medications. It can also be defined as physical symptoms, including tremor, slurred speech, akathesia, dystonia, anxiety, distress, paranoia, and bradyphrenia, that are primarily associated with improper dosing of or unusual reactions to neuroleptic (antipsychotic) medications.
Though they are commonly caused by the typical antipsychotics, but can also be caused by the atypical.
The adverse consequences of these syndromes can be minimized by vigilant clinicians who systematically examine patients at risk for these disorders and who manage them properly when discovered.
The best management is, of course, prevention, which starts with the judicious prescription of neuroleptics, and an awareness of the potential for certain nonpsychiatric medications to cause the same movement disorders.
Fibromyalgia is characterized by chronic widespread pain, increased tenderness at specific sites known as “tender points,” unrefreshing sleep, fatigue and cognitive dysfunction not attributable to other disease states.
Fibromyalgia affects 2–4% of the general population and of those affected, 80–90% are female. In general, symptom onset occurs between the ages of 30 and 60.
While the etiology of fibromyalgia is not entirely clear, associations with trauma, adverse life events, impaired mood (e.g., depression), anxiety, irritable bowel syndrome, irritable bladder syndrome, cold intolerance, paresthesias and other medical condition have been described. Consequently, a patient tailored approach to treatment is ideal to address both symptoms of fibromyalgia and any associated conditions.
Medication-induced movement disorder (Extra-Pyramidal Side Effects, EPSE) occurs due to treatment with antipsychotic medications. It can also be defined as physical symptoms, including tremor, slurred speech, akathesia, dystonia, anxiety, distress, paranoia, and bradyphrenia, that are primarily associated with improper dosing of or unusual reactions to neuroleptic (antipsychotic) medications.
Though they are commonly caused by the typical antipsychotics, but can also be caused by the atypical.
The adverse consequences of these syndromes can be minimized by vigilant clinicians who systematically examine patients at risk for these disorders and who manage them properly when discovered.
The best management is, of course, prevention, which starts with the judicious prescription of neuroleptics, and an awareness of the potential for certain nonpsychiatric medications to cause the same movement disorders.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
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CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
2. CONTENT
Introduction
Etiology
Pathophysiology
Signs and symptoms
Management
Current Clinical Practices At WSUCSH
Recommendations
2/19/2023
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3. Objectives
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Recognize signs and symptoms of schizophrenia
Explain potential pathophysiologic mechanisms
that are thought to underlie schizophrenia.
Identify treatment goals for a patient with
schizophrenia.
Recommend appropriate antipsychotic
medications based on patient-specific data.
Compare side effect profiles of individual
antipsychotics.
4. INTRODUCTION
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Schizophrenia literally means “Fragmented Mind”.
Schizophrenia is one of the most complex, chronic
and challenging of psychiatric disorders that affects
how a person thinks, feels, behaves.
It represents a heterogeneous syndrome of
disorganized thoughts, delusions, hallucinations,
and impaired psychosocial functioning.
The prevalence of schizophrenia ranges from 0.6%
to 1.9%, with an average of approximately
1%.(Reeves et al., 2011)
5. Cont...
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Prevalence is equal in men and women, but
symptoms appear earlier in men with first
hospitalization typically occurring at 15 to 24 years
compared to 25 to 34 years in women. (Saha et al.,
2005)
In Ethiopia the overall Prevalence were 0.4% and
0.3%, for schizophrenia 0.5% and 0.4% for
schizoaffective disorders, respectively.(Kassa and
Abajobir, 2018)
7. TYPES
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Paranoid schizophrenia
Common form of schizophrenia
Prominent hallucinations and/or delusions
Speech and emotions may be unaffected
At risk for suicidal or violent behavior under
influence of delusions
May develop at a later age than other types of
schizophrenia.
8. Cont.…
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Hebephrenic / Disorganized schizophrenia
Behavior is disorganized and without purpose
Thoughts are disorganized, difficult to understand by
others.
Delusions and hallucinations are fleeting
Usually develops between 15-25
Catatonic schizophrenia
Rarer than other types
At risk for malnutrition, exhaustion or self-injury
Unusual movements, often switching between extremes of
overactivity and stillness
Unable to talk (Catatonia)
9. Cont.…
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Undifferentiated schizophrenia
Some characteristics of paranoid, hebephrenic or
catatonic schizophrenia, but does not obviously fit
one of these types.
Residual schizophrenia
Past History of psychosis but only having negative
symptoms
12. Cont.…
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Glutamate Hypothesis
NMDA receptor hypofunction is thought to reduce the level
of activity in mesocortical dopaminergic neurons.
This would result in a decrease in dopamine release in the
prefrontal cortex and thus give rise to negative symptoms
of schizophrenia.
5-HT Hypothesis
Serotoninergic receptors are present on dopaminergic
axons and it is known that stimulation of these receptors
will decrease DA release in prefrontal cortex.
14. Cont.…
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The Diagnostic and Statistical Manual for Mental
Disorders (DSM-5) identifies five symptoms for
diagnosis
At least two of the following symptoms must be
present for at least 1 month, and at least one of
the symptoms should be
delusions, hallucinations, or disorganized speech.
Continuous signs of disturbance must be present
for at least 6 months.
16. Cont.…
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Clinical Management
Acute Phase (Initial Presentation) 4 to 8 weeks :
Defined by acute psychotic episode
Stabilization Phase (Early symptom remission) as
long as 3 months.
Stable Phase (Maintenance treatment) : Involves
stable treatment
17. Cont.…
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Pharmacotherapeutic algorithm for schizophrenia.
Stage 1A
Applies to those patients experiencing their first
acute episode of schizophrenia.
Studies suggest that the use of SGAs during the first
acute episode results in greater treatment retention
and are more effective in preventing a second
psychotic episode compared to FGAs. (Hasan et al.,
2013)
In addition, SGAs carry a reduced risk of EPS.
18. Cont.…
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Because first-episode patients demonstrate
greater sensitivity to adverse effects, antipsychotic
dosing should be initiated at the lower end of the
dose range.(Kane et al.)
Among the SGAs,aripiprazole, olanzapine,
quetiapine, risperidone, and ziprasidone have
evidence of efficacy in first-episode
patients.(Goldman et al., 2017)
19. Cont.…
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Stage 1B
addresses pharmacotherapy of a patient who was
previously treated with an antipsychotic, and
treatment is being restarted because the patient
stopped taking the medication.
If during the initial antipsychotic trial
the patient Experienced a robust improvement in
symptoms, good tolerability, and the patient is
positive about taking this antipsychotic again,
then that medication can be restarted.
20. Cont.…
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Stage 2
Addresses pharmacotherapy in a patient who had
inadequate clinical improvement with the
antipsychotic used in stage 1A or 1B.
Stage 2 recommends antipsychotic monotherapy
with an FGA or SGA not used in stage 1 or
stage1B.(Bajor et al., 2011)
Because of safety concerns and the need for white
blood cell (WBC) monitoring, clozapine is not
generally recommended at stage 2.(Bajor et al.,
2011)
21. Cont.…
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However, clozapine has superior efficacy in
decreasing suicidal behavior, and it should be
considered at stage 2 for the suicidal
patient.(Remington et al., 2017)
Clozapine can also be considered at stage 2 in
patients with a history of violence or comorbid
substance abuse.(Bajor et al., 2011)
Long-acting injectable antipsychotics(LAIAs)
should be considered as an optionat stage 2.
22. Cont.…
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Stage 3
Poor symptom improvement with two different
antipsychotic trials at appropriate dose and
duration.
the recommended treatment is clozapine.
stage 4
Only minimal evidence exists for any treatment
option for those patients who do not have
adequate symptom improvement with clozapine.
23. Initial Treatment in an Acute
Psychotic Episode
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The goals during the first 7 days of treatment should be
decreased agitation, hostility, anxiety, tension, and
aggression, and normalization of sleep and eating
patterns.
The usual recommendation is to initiate therapy and to
titrate the dose over the first few days to an average
effective dose.
Intramuscular (IM) antipsychotic administration (eg,
aripiprazole 5.25-9.75 mg IM, haloperidol 2-5 mg IM,
olanzapine 2.5-10 mg IM, or ziprasidone 10-20 mg IM) can
be used to assist in calming a severely agitated patient.
24. Cont.…
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If the patient is receiving an antipsychotic within
the usual therapeutic range, the use of lorazepam
2 mg IM as needed in combination with the
maintenance antipsychotic is a rational alternative
for treatment of aggression.
25. Stabilization Therapy
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Symptom improvement may occur over 6 to 12
weeks
During the first 2 to 3 weeks, goals should
include increased socialization and improvement
in self-care habits and mood.
In general, if a patient has shown no improvement
after 2 weeks of treatment at therapeutic doses
only a partial decrease in positive symptoms
within 8 to 12 weeks at adequate doses, then the
next algorithm stage should be considered.
26. Maintenance Treatment
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Maintenance drug therapy prevents relapse, as
shown in numerous double-blind studies, and
avoiding relapse is a major goal of treatment.
The average relapse rate after 1 year is 18% to
32% with active drug (including some
nonadherent patients) versus 60% to 80% for
placebo.(Bajor et al., 2011)
After treatment of the first psychotic episode in a
patient with schizophrenia, medication should be
continued for at least 18 months after
remission.(Remington et al., 2017)
27. Treatment Adherence
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Antipsychotic nonadherence is estimated to occur
in at least 40% to 50% of patients with
schizophrenia.
For patients who have
Relapsed several times because of nonadherence
have a history of dangerous behavior, or risk a
significant loss of social or vocational gains when
relapsed
treatment with long-acting injection (LAI) should
be encouraged.
31. Adjunct Treatments
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Pharmacologic therapies other than
antipsychotics is often necessary for the treatment
of motor side effects, anxiety, depression, mood
elevation.
Anticholinergic medications (eg, benztropine, 1–2
mg twice daily; trihexyphenidyl, 1–3 mg thrice
daily; and diphenhydramine, 25–50 mg twice
daily) are used to treat EPS.
β-Blockers (eg, propranolol 30–120 mg/day) are
sometimes effective for patients who develop
akathisia.
32. CONTROVERSY
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With the introduction of SGAs in the 1990s, the use of
FGAs has progressively decreased, and FGAs have less than
10% market share of the antipsychotics used for
schizophrenia.
This decline occurred because of the touted better side
effect profile and other possible benefits of SGAs in
nonpsychotic domains of the illness.
However, a large landmark study (the Clinical
Antipsychotics Trials of Intervention Effectiveness [CATIE
trial]; The study revealed that the FGA was equal to the
SGAs for the primary endpoint of time to discontinuation
of medication. (Lieberman et al., 2005)
33. Cont.…
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SGAs have historically been much more expensive than the
FGAs
When selecting an antipsychotic, the risk-to-benefit profile
becomes fundamental and the varying side effect profiles
must be considered.
Early studies did not consistently demonstrate an
advantage of long-acting injectable antipsychotics (LAIAs)
over oral agents.
In contrast,recent studies, designed to reflect real-world
practices, have more consistently demonstrated an
advantage in reduced hospitalizations and relapse
prevention in patients with schizophrenia.(Citrome, 2013)
34. Cont.…
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34
Combining an FGA with an SGA and combining different
SGAs have been suggested as intervention strategies for
treatment-resistant patients.
there is limited rationale to explain how combinations of
antipsychotics would produce enhanced efficacy, but
increased side effects, particularly increased EPS,
metabolic effects, and hyperprolactinemia, are possible
results.
The evidence to support antipsychotic combinations is
scant at best, and recent treatment guidelinesstate that
there is insufficient evidence to support this
practice.(Remington et al., 2017)
35. Current Clinical Practices At
WSUCSH
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Emergency phase
First line Haloperidol, 5-10mg I.M./I.V. over 30-60 minutes. Daily dose
may go as high as 40mg.
Stabilization phase
First line Haloperidol, 1-15mg/day P.O.
Alternative Chlorpromazine, 75-300mg/P.O., in divided doses.
Maintenance (chronic therapy)
First line Haloperidol, 1-15mg/day P.O.
Alternatives Chlorpromazine, 75-300mg/day P.O. QD. in divided doses.
OR Fluphenazine decanoate, 12.5-100mg IM every 3-4 weeks
Adjunct treatment
Trihexyphenidyl, oral, initial 1 mg/day; increase as necessary to usual
range: 5-15mg/day in 3-4 divided doses
36. Recommendations
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For Multi-disciplinary Team
Monitor appropriate laboratory measures to prevent or minimize
adverse effects, including metabolic abnormalities
For clinical pharmacist team
Educate patient and caregiver (with patient consent) about the illness,
medication treatments, possible side effects, and goals of treatment.
Discuss medication adherence and healthy lifestyle goals, including
substance and cigarette use.
Select or optimize the dose of an antipsychotic based on the side effect
profile that is most appropriate and acceptable to the patient.