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INTRODUCTION TO
PSYCHOTROPIC DRUGS
Prepared by,
Mr. Larry Lee Lian Seng (Pegawai Farmasi UF 48)
CONTENTS
2
1) Basic Pharmacology
2) Medications for Schizophrenia
3) Medications for Depression/Anxiety
4) Medications for Bipolar Disorders
5) Medications for Sleep (Anxiolytic)
BASIC
PHARMACOLOGY
3
1
BASIC PHARMACOLOGY
▰ Psychotropic drugs are chemical substances
that can change brain function and result in
alterations in perceptions, mood,
consciousness, cognition, or behaviour.
4
"CHAPTER 1 Alcohol and Other Drugs". ISBN 0-7245-3361-3. Archived from the original on 2015-03-28.
BASIC PHARMACOLOGY
• In general,medication should be started at the lowest
possible dose and gradually increased to the lowest
effective dose
– Many adverse effects are dose dependent
– Some medications require monitoring of blood levels
for effective levels and to prevent toxic levels
5
BASIC PHARMACOLOGY
• In general, when stopping a medication, slowly
decreasing the dose decreases the risk of
discontinuation symptoms
– In some cases of adverse reactions medications
must be stopped immediately.
6
BASIC PHARMACOLOGY
• Medications can interact with each other, some foods, or
street drugs in ways which change how they act, how
long or short they act, how toxic they are, and how high a
dose is needed
• Medications can act synergistically in causing adverse
effects including risk of overdose.
7
MEDICATIONS FOR
SCHIZOPHRENIA
8
2
MEDICATIONS FOR SCHIZOPHRENIA
▰ TYPICAL
▰ Haloperidol
▰ Chlorpromazine
▰ Sulpiride
▰ Zuclopenthixol (Depot)
▰ Flupenthixol (Depot)
▰ Trifluoperazine
▰ Fluphenazine
▰ Perphenazine
▰ ATYPICAL
▰ Clozapine
▰ Risperidone
▰ Aripiprazole
▰ Olanzapine
▰ Quetiapine
▰ Amisulpride
▰ Asenapine
▰ Paliperidone (Depot)
▰ Ziprasidone
9
10
CHOICE OF ANTIPSYCHOTICS
▰ Should be based on the
agreement between people
with schizophrenia and
clinicians taking into
account the relative
benefits of the drugs and
their side-effect profiles.
11
Risks
Benefits
“
MECHANISM ACTION OF
ANTIPSYCHOTICS
1
MECHANISM OF ANTIPSYCHOTICS
▰
13
FIRST GENERATION ANTIPSYCHOTIC SECOND GENERATION ANTIPSYCHOTIC
D2 Antagonism 5HT2A / D2 Antagonism
Meltzer HY, Matsubara S, Lee JC. The ratios of 5HT2 and D2 affinities differentiate
atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390-2.
D2
ANTAGONIST
Mesolimbic pathway
dramatic therapeutic action
on positive psychotic
symptoms
Tuberoinfundibular pathway
hyperprolactinemia (lactation,
infertility, sexual dysfunction)
Nigrostriatal pathway
extrapyramidal side effects
(EPS) and tardive dyskinesia
Mesocortical pathway
enhanced negative and
cognitive psychotic
symptoms
SIDE EFFECTS OF TYPICAL ANTIPSYCHOTICS
(1ST Generation)
MOTOR SIDE EFFECTS
▻ Tardive dyskinesia
▻ Parkinsonism
▻ Dystonia
▻ Akathisia
AUTONOMIC SIDE EFFECTS
▻ Othostatic hypotension
▻ Tachycardia
▻ Constipation
▻ Urinary retention
▻ Sexual dysfunction 15
PSYCHIATRIC SIDE EFFECTS
▻ Sedation
▻ Apathy
▻ Confusion
ATYPICAL ANTIPSYCHOTIC (2nd Generation)
▰ Atypical antipsychotics have mostly replaced the older
antipsychotic for treating schizophrenia, BD, and other
severe mental illness because of their many advantages.
▻ Lower tendency for causing parkinsonism
▻ More effective when treating the negative symptoms of
schizophrenia
▻ Better patient acceptability
▰ There are heterogeneous group of medicines with different
properties and side effects. 16
SIDE EFFECTS OF ATYPICAL ANTIPSYCHOTIC (2nd Generation)
ANTIPSYC
HOTICS
Aripiprazole Olanzapine Quetiapine Risperidone Clozapine Amisulpiride
Potential
advantage
- Very low
sedation
- Long Half-life
- Lower
metabolic
syndrome
- Possible
greater efficacy
- Sedating
- Low EPS
- Sedating
- Possible
greater
efficacy
- Effective in TR
schizophrenia
- Lower
metabolic
syndrome
Side effect - Highest
akathisia
- Worst
metabolic
profile
- High weight
gain
- Metabolic
profile
- Sedating
- Weight gain
- Postural
hypotension
- Highest
prolactin
elevation
-Parkinsonism
with high
doses
- Metabolic
profile
- Agranulositosis
- Hypersalivation
- Sedation
- Postural
hypotension
- Anticholinergic
side effects
- Parkinsonism
with high doses
-
Hyperprolactine
mia
- High sexual
dysfunction
“Choice of antipsychotic medication should be made
by the patient and physician TOGETHER, taking into
account views of a carer where appropriate.
Provide information and discuss the likely benefits
and side effects of each drug.
(NICE Guideline for Schizophrenia Treatment)
18
18
National Institute for Health and Care Excellence. Schizophrenia: core interventions in the treatment and management of
schizophrenia in adults in primary and secondary care (update). Clinical Guideline 82, 2009.
https://www.nice.org.uk/guidance/cg82.
MEDICATIONS FOR
DEPRESSION / ANXIETY
19
3
PRINCIPLES OF PHARMACOLOGIC TREATMENT OF MDD
▰ General principles of MDD treatment are:
▻ to relieve symptoms
▻ to reduce the morbidity and disability
▻ to limit risks of self-harm and fatality
20
CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
DRUGS USED IN THE TREATMENT OF MDD
21
CLASS EXAMPLES
Tricyclic Antidepressants Amitryptyline, Dothiepine, Clomipramine, Imipramine,
Mianserin, Nortriptyline
Monoamine Oxidase Inhibitors (MAOIs) Phenelzine, Moclobemide
Selective Serotonin Reuptake Inhibitors (SSRI) Sertraline, Fluvoxamine, Escitalopram, Fluoxetine,
Paroxetine
Serotonin Noradrenaline Reuptake Inhibitor (SNRI) Venlafaxine, Desvenlafaxine, Duloxetine
Noradrenergic and Specific
Serotonergic Antidepressants (NaSSAs)
Mirtazapine
Multimodal Serotonin Modulator Antidepressant Vortioxetine
Melatonergic Agonist and Serotogenic Antagonist
Antidepressant
Agomelatine
CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
22
PRINCIPLES OF PHARMACOLOGIC TREATMENT OF MDD
▰ The choice of antidepressant medication will depend on
various factors including:
▻ efficacy and tolerability
▻ patient profile and comorbidities
▻ concomitant medications
▻ drug-drug interactions
▻ cost and availability
▻ patients’ preference
23
CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
PRINCIPLES OF PHARMACOLOGIC TREATMENT OF MDD
▰ Most second-generation antidepressants namely
SSRIs, SNRIs, NaSSAs, melatonergic and multimodal
antidepressant may be considered as the initial
treatment medication.
▰ The older antidepressants such as TCAs and MAOIs
are considered for subsequent choice later.
24
CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
PRINCIPLES OF PHARMACOLOGIC TREATMENT
▰Start low, go slow……BUT GET THERE!
▰Monitor ADHERENCE.
▰CYP 450 interactions, sedation, concomitant
medical illness are issues to consider.
25
Depression of the Elderly, Jackie L. Neel, D.O.
PHASES OF TREATMENT
A) Acute Phase
Antidepressants given until remission is achieved.
B) Continuation Phase
The duration of continuation phase treatment is generally 6-9 months
from the acute phase. With risk factors, > 2 years
C) Maintenance Phase
This is a period to prevent recurrence and the optimal duration is difficult
to determine because some patients require a longer period and some an
indefinite period.
26
Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guide_x0002_lines for
the management of major depressive disorder in adults: III. Pharmacotherapy. J Affect Disord. 2009;117(Suppl 1):S26-S43.
ANTIDEPRESSANT SIDE EFFECTS & MANAGEMENTS*
27
Adverse Effect Coping Strategies
Nausea • Take with food or divide the dose (half with breakfast, half with lunch)
• Suck on sugarless hard candy
• Drink plenty of fluids
• Try antacids
Fatigue, drowsiness • Brief nap during the day
• Regular physical activity
• Avoid driving or operating dangerous machinery until the fatigue passes
• Take ATD 1 to 2 two hours before bedtime
Insomnia • Take ATD in the morning
• Avoid caffeinated food and drinks
• Regular physical activity
Dizziness • Rise slowly from sitting
• Use handrails, canes or other sturdy items for support
• Avoid driving or operating machinery
• Avoid caffeine, tobacco and alcohol
• Drink plenty of fluids
• Take the antidepressant at bedtime
ANTIDEPRESSANT SIDE EFFECTS & MANAGEMENTS*
28
Adverse Effect Coping Strategies
Dry mouth • Sip water regularly or suck on ice chips
• Chew sugarless gum or suck on sugarless hard candy
• Avoid caffeine
• Breathe through your nose, not your mouth
• Brush teeth twice daily, floss daily and see dentist regularly
• Consider a moisturizing mouth spray or another product that might stimulate saliva production
Blurry Vision • Consider use of eye drops to relieve dryness
• Get an eye exam to see whether blurred vision caused by an antidepressant may be worsened by an
underlying eye problem
• Consider alternative antidepressant
Constipation • Drink plenty of water
• Eat high-fiber foods or a fiber supplement
• Get regular exercise
• Consider stool softeners
Agitation,
restlessness, anxiety
• Get regular exercise
• Practice deep-breathing exercises, muscle relaxation or yoga
• Consider switching to an antidepressant that is not as stimulating
ANTIDEPRESSANT SIDE EFFECTS & MANAGEMENTS*
▰ Simon G, et al. Unipolar major depression in adults: Choosing initial treatment. https://www.uptodate.com/contents/search. Accessed Aug. 23, 2019.
▰ Tarleton EK, et al. Primer for nutritionists: Managing the side effects of antidepressants. Clinical Nutrition ESPEN. 2016; doi:10.1016/j.clnesp.2016.05.004
▰ Mental healthmedications. National Institute of Mental Health. http://www.nimh.nih.gov/health/publications/mental-health-medications/index.shtml. Accessed Aug. 23, 2019.
▰ Morgan AJ, et al. Self-help strategies for sub-threshold anxiety: A Delphi consensus study to find messages suitable for population-wide promotion. Journal of Affective Disorders. 2018;
doi:10.1016/j.jad.2016.07.024.
▰ Nassan M, et al. Pharmacokinetic pharmacogenetic prescribing guidelines for antidepressants: A template for psychiatric precision medicine. Mayo Clinic Proceedings. 2016;
doi:10.1016/j.mayocp.2016.02.023.
▰ LeBlanc A, et al. Shared decision making for antidepressants in primary care: A cluster randomized trial. JAMA Internal Medicine. 2015; doi:10.1001/jamainternmed.2015.5214.
▰ Hirsch M, et al. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. https://www.uptodate.com/contents/search. Accessed Aug. 23, 2019.
▰ Celexa (prescribing information). Allergan USA, Inc.; 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020822s047lbl.pdf#page=33. Accessed Aug. 27, 2019.
▰ Dry mouth. National Institute of Dental and Craniofacial Research. https://www.nidcr.nih.gov/health-info/dry-mouth. Accessed Aug. 26, 2019.
▰ Kahl KG, et al. Effectsof psychopharmacological treatment withantidepressantson the vascular system. Vascular Pharmacology. 2017; doi:10.1016/j.vph.2017.07.004.
▰ Wang S-M, et al. Addressing the side effects of contemporary antidepressant drugs: A comprehensive review. Chonnam Medical Journal. 2018; doi:10.4068/cmj.2018.54.2.101.
▰ Postural hypotension: What it is and how to manage it. Centers for Disease Control and Prevention. https://www.cdc.gov/steadi/patient.html. Accessed Aug. 26, 2019.
▰ Constipation. Merck Manual Professional Version. https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gi-disorders/constipation. Accessed Aug. 26, 2019.
▰ Tainted sexual enhancement products. U.S. Food and Drug Administration. https://www.fda.gov/drugs/medication-health-fraud/tainted-sexual-enhancement-products. Accessed Aug. 27, 2019.
29
MEDICATIONS FOR
BIPOLAR DISORDER
30
4
PRINCIPLES OF PHARMACOLOGIC TREATMENT
OF BIPOLAR DISORDER
▰ The main biological treatments used are:
▻ Antipsychotic medications
▻ Mood stabilising agents
▻ GABA agonists (e.g., Benzodiazepines)
▻ Antidepressants
▻ Complimentary therapies
31
Goodwin, G.M., Haddad, P.M., Ferrier, I. N., Aronson, J. K., Barnes, T. R. H., Cipriani, A., Holmes, E. A. (2016). Evidence-based
guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology.
Journal of Psychopharmacology, 30(6), 495-553.
TREATMENT OR BIPOLAR DISORDER
32
CPG of the Management of Bipolar Disorder
in Adults, 2014
MOOD STABILISERS
▰ Lithium
▰ Sodium Valproate
▰ Carbamazepine
▰ Lamotrigine
33
34
“Both LITHIUM & SODIUM
VALPROATE require TDM to
ensure the safe and effective
use of the medicatios.
35
35
National Institute for Health and Care Excellence. Schizophrenia: core interventions in the treatment and management of
schizophrenia in adults in primary and secondary care (update). Clinical Guideline 82, 2009.
https://www.nice.org.uk/guidance/cg82.
LITHIUM
36
▰ Inhibits EXCITATORY neurotransmitters such as Dopamine and
Glutamate by blocking their receptors.
▰ Promotes GABA-mediated neurotransmission.
1) Malhi, G. S., Tanious, M., Das, P., Coulston, C. M., & Berk, M. (2013). Potential mechanisms of action of lithium in bipolar disorder. CNS
drugs, 27(2), 135-153.
2) CPG of the Management of Bipolar Disorder in Adults, 2014
SODIUM VALPROATE
37
▰ Increasing GABAergic neurotransmission.
▰ As GABA is an inhibitory neurotransmitter, this increase results in increased
inhibitory activity.Promotes GABA-mediated neurotransmission.
1) Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting
polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012
May 15. [PubMed:22541068]
2) CPG of the Management of Bipolar Disorder in Adults, 2014
SODIUM VALPROATE
38
TERATOGENICITY
SODIUM VALPROATE
39
▰ Mood stabilisers can be teratogenic.
▰ Sodium valproate is of particular concern, as 10–11% of infants
exposed in utero will have major congenital malformations and
are at risk of significant intellectual impairment.
▰ Sodium valproate should not be used as a first line mood
stabiliser in women of child bearing age.
1. Khan SJ, Fersh ME, Ernst C, et al. (2016) Bipolar disorder in pregnancy and postpartum: Principles of management. Current Psychiatry Reports 18: 13.
2. Tomson T and Battino D (2012) Teratogenic effects of antiepileptic drugs. The Lancet Neurology 11: 803–813
3. Gentile S (2014) Risks of neurobehavioral teratogenicity associated with prenatal exposure to valproate monotherapy: A systematic review with regulatory
repercussions. CNS Spectrums 19: 305–315.
4. Malhi GS, Bassett D, Boyce P, et al. (2015) Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders.
Australian and New Zealand Journal of Psychiatry 49: 1087–1206.
MEDICATIONS FOR SLEEP
40
5
BENZODIAZEPINES
41
▰ Increasing the inhibitory effect of GABA on neuronal excitability
BENZODIAZEPINES AVAILABLE IN KKM FORMULARY
42
DOSE EQUIVALENT
43
Drug Daily range
mg
Equiv 5mg
diazepam.
Duration (½ life)
Midazolam 5 – 1 0 2 Short
Alprazolam 0.25 – 4 0.5 - 1
Short/Intermediate
Bromazepam 6 – 30 3 – 6
Lorazepam 2 – 6 1
Clobazam 5 – 80 1 0
Intermediate
Clonazepam 0.5 – 4 0.5
Nitrazepam 5 – 1 0 5 – 1 0
Diazepam 2 – 40 5 Long
Short : 3 – 8 hours
Intermediate : 1 0 – 20 hours
Long : 1 – 3 days *Lexicomp Drug Dictionary
SIDE EFFECTS OF BENZODIAZEPINES
44
• Headaches
• Confusion
• Ataxia (Disorders that affects coordination, balance and speech)
• Dysarthria (Difficulty speaking)
• Blurred vision
• GI disturbances
• Paradoxical excitement
• Impair cognition (e.g., memory, attention and processing speed)
23 Crowe SF et al. The residual medium and long‐term cognitive effects of benzodiazepine use: an updated
meta‐analysis. Arch Clin Neuropsychol 2017; doi: 10.1093/arclin/acx120. [Epub ahead of print]
APPROPRIATE USE OF BENZODIAZEPINES
● Benzodiazepines provide rapid symptomatic relief from
acute anxiety states.
● Only use for severe anxiety, disabling or in extreme
distress.
● Use lowest effective dose + shortest time (max 4 weeks).
● Caution in patients with substance misuse.
45
Department of Health (DoH). Benzodiazepines: Good Practice Guidelines for Clinicians (2002).Accessed at
www.health.gov.ie/wp-content/uploads/2014/04/Benzodiazepines-Good Practice-Guidelines.pdf on 14 February
2017.
CONCLUSION
PHARMACIST’S ROLES
▰ There is so much that we can do to improve patient’s
quality of life.
▰ It all begins with patient being able to adhere to
medication.
47
PHARMACIST’S ROLES
▰ Pharmacists have the potential to have a large effect in enhancing
patient’s quality of life through a variety of interventions such as :1
▻ reducing the number of medications taken
▻ reducing the number of doses taken, increasing patient adherence,
▻ preventing adverse drug reactions (ADRs),
▻ improving patient quality of life and
▻ decreasing facility and drug costs.
48
1. Chumney EC, Robinson LC. The effects of pharmacist interventions on patients with polypharmacy. Pharm Pract
(Granada). 2006 Jul;4(3):103-9. PMID: 25247007; PMCID: PMC4156841.
THANK YOU!

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INTRODUCTION TO PSYCHOTROPIC DRUGS.ppt

  • 1. INTRODUCTION TO PSYCHOTROPIC DRUGS Prepared by, Mr. Larry Lee Lian Seng (Pegawai Farmasi UF 48)
  • 2. CONTENTS 2 1) Basic Pharmacology 2) Medications for Schizophrenia 3) Medications for Depression/Anxiety 4) Medications for Bipolar Disorders 5) Medications for Sleep (Anxiolytic)
  • 4. BASIC PHARMACOLOGY ▰ Psychotropic drugs are chemical substances that can change brain function and result in alterations in perceptions, mood, consciousness, cognition, or behaviour. 4 "CHAPTER 1 Alcohol and Other Drugs". ISBN 0-7245-3361-3. Archived from the original on 2015-03-28.
  • 5. BASIC PHARMACOLOGY • In general,medication should be started at the lowest possible dose and gradually increased to the lowest effective dose – Many adverse effects are dose dependent – Some medications require monitoring of blood levels for effective levels and to prevent toxic levels 5
  • 6. BASIC PHARMACOLOGY • In general, when stopping a medication, slowly decreasing the dose decreases the risk of discontinuation symptoms – In some cases of adverse reactions medications must be stopped immediately. 6
  • 7. BASIC PHARMACOLOGY • Medications can interact with each other, some foods, or street drugs in ways which change how they act, how long or short they act, how toxic they are, and how high a dose is needed • Medications can act synergistically in causing adverse effects including risk of overdose. 7
  • 9. MEDICATIONS FOR SCHIZOPHRENIA ▰ TYPICAL ▰ Haloperidol ▰ Chlorpromazine ▰ Sulpiride ▰ Zuclopenthixol (Depot) ▰ Flupenthixol (Depot) ▰ Trifluoperazine ▰ Fluphenazine ▰ Perphenazine ▰ ATYPICAL ▰ Clozapine ▰ Risperidone ▰ Aripiprazole ▰ Olanzapine ▰ Quetiapine ▰ Amisulpride ▰ Asenapine ▰ Paliperidone (Depot) ▰ Ziprasidone 9
  • 10. 10
  • 11. CHOICE OF ANTIPSYCHOTICS ▰ Should be based on the agreement between people with schizophrenia and clinicians taking into account the relative benefits of the drugs and their side-effect profiles. 11 Risks Benefits
  • 13. MECHANISM OF ANTIPSYCHOTICS ▰ 13 FIRST GENERATION ANTIPSYCHOTIC SECOND GENERATION ANTIPSYCHOTIC D2 Antagonism 5HT2A / D2 Antagonism Meltzer HY, Matsubara S, Lee JC. The ratios of 5HT2 and D2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390-2.
  • 14. D2 ANTAGONIST Mesolimbic pathway dramatic therapeutic action on positive psychotic symptoms Tuberoinfundibular pathway hyperprolactinemia (lactation, infertility, sexual dysfunction) Nigrostriatal pathway extrapyramidal side effects (EPS) and tardive dyskinesia Mesocortical pathway enhanced negative and cognitive psychotic symptoms
  • 15. SIDE EFFECTS OF TYPICAL ANTIPSYCHOTICS (1ST Generation) MOTOR SIDE EFFECTS ▻ Tardive dyskinesia ▻ Parkinsonism ▻ Dystonia ▻ Akathisia AUTONOMIC SIDE EFFECTS ▻ Othostatic hypotension ▻ Tachycardia ▻ Constipation ▻ Urinary retention ▻ Sexual dysfunction 15 PSYCHIATRIC SIDE EFFECTS ▻ Sedation ▻ Apathy ▻ Confusion
  • 16. ATYPICAL ANTIPSYCHOTIC (2nd Generation) ▰ Atypical antipsychotics have mostly replaced the older antipsychotic for treating schizophrenia, BD, and other severe mental illness because of their many advantages. ▻ Lower tendency for causing parkinsonism ▻ More effective when treating the negative symptoms of schizophrenia ▻ Better patient acceptability ▰ There are heterogeneous group of medicines with different properties and side effects. 16
  • 17. SIDE EFFECTS OF ATYPICAL ANTIPSYCHOTIC (2nd Generation) ANTIPSYC HOTICS Aripiprazole Olanzapine Quetiapine Risperidone Clozapine Amisulpiride Potential advantage - Very low sedation - Long Half-life - Lower metabolic syndrome - Possible greater efficacy - Sedating - Low EPS - Sedating - Possible greater efficacy - Effective in TR schizophrenia - Lower metabolic syndrome Side effect - Highest akathisia - Worst metabolic profile - High weight gain - Metabolic profile - Sedating - Weight gain - Postural hypotension - Highest prolactin elevation -Parkinsonism with high doses - Metabolic profile - Agranulositosis - Hypersalivation - Sedation - Postural hypotension - Anticholinergic side effects - Parkinsonism with high doses - Hyperprolactine mia - High sexual dysfunction
  • 18. “Choice of antipsychotic medication should be made by the patient and physician TOGETHER, taking into account views of a carer where appropriate. Provide information and discuss the likely benefits and side effects of each drug. (NICE Guideline for Schizophrenia Treatment) 18 18 National Institute for Health and Care Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in adults in primary and secondary care (update). Clinical Guideline 82, 2009. https://www.nice.org.uk/guidance/cg82.
  • 20. PRINCIPLES OF PHARMACOLOGIC TREATMENT OF MDD ▰ General principles of MDD treatment are: ▻ to relieve symptoms ▻ to reduce the morbidity and disability ▻ to limit risks of self-harm and fatality 20 CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
  • 21. DRUGS USED IN THE TREATMENT OF MDD 21 CLASS EXAMPLES Tricyclic Antidepressants Amitryptyline, Dothiepine, Clomipramine, Imipramine, Mianserin, Nortriptyline Monoamine Oxidase Inhibitors (MAOIs) Phenelzine, Moclobemide Selective Serotonin Reuptake Inhibitors (SSRI) Sertraline, Fluvoxamine, Escitalopram, Fluoxetine, Paroxetine Serotonin Noradrenaline Reuptake Inhibitor (SNRI) Venlafaxine, Desvenlafaxine, Duloxetine Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs) Mirtazapine Multimodal Serotonin Modulator Antidepressant Vortioxetine Melatonergic Agonist and Serotogenic Antagonist Antidepressant Agomelatine CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
  • 22. 22
  • 23. PRINCIPLES OF PHARMACOLOGIC TREATMENT OF MDD ▰ The choice of antidepressant medication will depend on various factors including: ▻ efficacy and tolerability ▻ patient profile and comorbidities ▻ concomitant medications ▻ drug-drug interactions ▻ cost and availability ▻ patients’ preference 23 CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
  • 24. PRINCIPLES OF PHARMACOLOGIC TREATMENT OF MDD ▰ Most second-generation antidepressants namely SSRIs, SNRIs, NaSSAs, melatonergic and multimodal antidepressant may be considered as the initial treatment medication. ▰ The older antidepressants such as TCAs and MAOIs are considered for subsequent choice later. 24 CPG of Management of Major Depressive Disorder (2nd Edition), June 2019
  • 25. PRINCIPLES OF PHARMACOLOGIC TREATMENT ▰Start low, go slow……BUT GET THERE! ▰Monitor ADHERENCE. ▰CYP 450 interactions, sedation, concomitant medical illness are issues to consider. 25 Depression of the Elderly, Jackie L. Neel, D.O.
  • 26. PHASES OF TREATMENT A) Acute Phase Antidepressants given until remission is achieved. B) Continuation Phase The duration of continuation phase treatment is generally 6-9 months from the acute phase. With risk factors, > 2 years C) Maintenance Phase This is a period to prevent recurrence and the optimal duration is difficult to determine because some patients require a longer period and some an indefinite period. 26 Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guide_x0002_lines for the management of major depressive disorder in adults: III. Pharmacotherapy. J Affect Disord. 2009;117(Suppl 1):S26-S43.
  • 27. ANTIDEPRESSANT SIDE EFFECTS & MANAGEMENTS* 27 Adverse Effect Coping Strategies Nausea • Take with food or divide the dose (half with breakfast, half with lunch) • Suck on sugarless hard candy • Drink plenty of fluids • Try antacids Fatigue, drowsiness • Brief nap during the day • Regular physical activity • Avoid driving or operating dangerous machinery until the fatigue passes • Take ATD 1 to 2 two hours before bedtime Insomnia • Take ATD in the morning • Avoid caffeinated food and drinks • Regular physical activity Dizziness • Rise slowly from sitting • Use handrails, canes or other sturdy items for support • Avoid driving or operating machinery • Avoid caffeine, tobacco and alcohol • Drink plenty of fluids • Take the antidepressant at bedtime
  • 28. ANTIDEPRESSANT SIDE EFFECTS & MANAGEMENTS* 28 Adverse Effect Coping Strategies Dry mouth • Sip water regularly or suck on ice chips • Chew sugarless gum or suck on sugarless hard candy • Avoid caffeine • Breathe through your nose, not your mouth • Brush teeth twice daily, floss daily and see dentist regularly • Consider a moisturizing mouth spray or another product that might stimulate saliva production Blurry Vision • Consider use of eye drops to relieve dryness • Get an eye exam to see whether blurred vision caused by an antidepressant may be worsened by an underlying eye problem • Consider alternative antidepressant Constipation • Drink plenty of water • Eat high-fiber foods or a fiber supplement • Get regular exercise • Consider stool softeners Agitation, restlessness, anxiety • Get regular exercise • Practice deep-breathing exercises, muscle relaxation or yoga • Consider switching to an antidepressant that is not as stimulating
  • 29. ANTIDEPRESSANT SIDE EFFECTS & MANAGEMENTS* ▰ Simon G, et al. Unipolar major depression in adults: Choosing initial treatment. https://www.uptodate.com/contents/search. Accessed Aug. 23, 2019. ▰ Tarleton EK, et al. Primer for nutritionists: Managing the side effects of antidepressants. Clinical Nutrition ESPEN. 2016; doi:10.1016/j.clnesp.2016.05.004 ▰ Mental healthmedications. National Institute of Mental Health. http://www.nimh.nih.gov/health/publications/mental-health-medications/index.shtml. Accessed Aug. 23, 2019. ▰ Morgan AJ, et al. Self-help strategies for sub-threshold anxiety: A Delphi consensus study to find messages suitable for population-wide promotion. Journal of Affective Disorders. 2018; doi:10.1016/j.jad.2016.07.024. ▰ Nassan M, et al. Pharmacokinetic pharmacogenetic prescribing guidelines for antidepressants: A template for psychiatric precision medicine. Mayo Clinic Proceedings. 2016; doi:10.1016/j.mayocp.2016.02.023. ▰ LeBlanc A, et al. Shared decision making for antidepressants in primary care: A cluster randomized trial. JAMA Internal Medicine. 2015; doi:10.1001/jamainternmed.2015.5214. ▰ Hirsch M, et al. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. https://www.uptodate.com/contents/search. Accessed Aug. 23, 2019. ▰ Celexa (prescribing information). Allergan USA, Inc.; 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020822s047lbl.pdf#page=33. Accessed Aug. 27, 2019. ▰ Dry mouth. National Institute of Dental and Craniofacial Research. https://www.nidcr.nih.gov/health-info/dry-mouth. Accessed Aug. 26, 2019. ▰ Kahl KG, et al. Effectsof psychopharmacological treatment withantidepressantson the vascular system. Vascular Pharmacology. 2017; doi:10.1016/j.vph.2017.07.004. ▰ Wang S-M, et al. Addressing the side effects of contemporary antidepressant drugs: A comprehensive review. Chonnam Medical Journal. 2018; doi:10.4068/cmj.2018.54.2.101. ▰ Postural hypotension: What it is and how to manage it. Centers for Disease Control and Prevention. https://www.cdc.gov/steadi/patient.html. Accessed Aug. 26, 2019. ▰ Constipation. Merck Manual Professional Version. https://www.merckmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gi-disorders/constipation. Accessed Aug. 26, 2019. ▰ Tainted sexual enhancement products. U.S. Food and Drug Administration. https://www.fda.gov/drugs/medication-health-fraud/tainted-sexual-enhancement-products. Accessed Aug. 27, 2019. 29
  • 31. PRINCIPLES OF PHARMACOLOGIC TREATMENT OF BIPOLAR DISORDER ▰ The main biological treatments used are: ▻ Antipsychotic medications ▻ Mood stabilising agents ▻ GABA agonists (e.g., Benzodiazepines) ▻ Antidepressants ▻ Complimentary therapies 31 Goodwin, G.M., Haddad, P.M., Ferrier, I. N., Aronson, J. K., Barnes, T. R. H., Cipriani, A., Holmes, E. A. (2016). Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 30(6), 495-553.
  • 32. TREATMENT OR BIPOLAR DISORDER 32 CPG of the Management of Bipolar Disorder in Adults, 2014
  • 33. MOOD STABILISERS ▰ Lithium ▰ Sodium Valproate ▰ Carbamazepine ▰ Lamotrigine 33
  • 34. 34
  • 35. “Both LITHIUM & SODIUM VALPROATE require TDM to ensure the safe and effective use of the medicatios. 35 35 National Institute for Health and Care Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in adults in primary and secondary care (update). Clinical Guideline 82, 2009. https://www.nice.org.uk/guidance/cg82.
  • 36. LITHIUM 36 ▰ Inhibits EXCITATORY neurotransmitters such as Dopamine and Glutamate by blocking their receptors. ▰ Promotes GABA-mediated neurotransmission. 1) Malhi, G. S., Tanious, M., Das, P., Coulston, C. M., & Berk, M. (2013). Potential mechanisms of action of lithium in bipolar disorder. CNS drugs, 27(2), 135-153. 2) CPG of the Management of Bipolar Disorder in Adults, 2014
  • 37. SODIUM VALPROATE 37 ▰ Increasing GABAergic neurotransmission. ▰ As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity.Promotes GABA-mediated neurotransmission. 1) Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068] 2) CPG of the Management of Bipolar Disorder in Adults, 2014
  • 39. SODIUM VALPROATE 39 ▰ Mood stabilisers can be teratogenic. ▰ Sodium valproate is of particular concern, as 10–11% of infants exposed in utero will have major congenital malformations and are at risk of significant intellectual impairment. ▰ Sodium valproate should not be used as a first line mood stabiliser in women of child bearing age. 1. Khan SJ, Fersh ME, Ernst C, et al. (2016) Bipolar disorder in pregnancy and postpartum: Principles of management. Current Psychiatry Reports 18: 13. 2. Tomson T and Battino D (2012) Teratogenic effects of antiepileptic drugs. The Lancet Neurology 11: 803–813 3. Gentile S (2014) Risks of neurobehavioral teratogenicity associated with prenatal exposure to valproate monotherapy: A systematic review with regulatory repercussions. CNS Spectrums 19: 305–315. 4. Malhi GS, Bassett D, Boyce P, et al. (2015) Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Australian and New Zealand Journal of Psychiatry 49: 1087–1206.
  • 41. BENZODIAZEPINES 41 ▰ Increasing the inhibitory effect of GABA on neuronal excitability
  • 42. BENZODIAZEPINES AVAILABLE IN KKM FORMULARY 42
  • 43. DOSE EQUIVALENT 43 Drug Daily range mg Equiv 5mg diazepam. Duration (½ life) Midazolam 5 – 1 0 2 Short Alprazolam 0.25 – 4 0.5 - 1 Short/Intermediate Bromazepam 6 – 30 3 – 6 Lorazepam 2 – 6 1 Clobazam 5 – 80 1 0 Intermediate Clonazepam 0.5 – 4 0.5 Nitrazepam 5 – 1 0 5 – 1 0 Diazepam 2 – 40 5 Long Short : 3 – 8 hours Intermediate : 1 0 – 20 hours Long : 1 – 3 days *Lexicomp Drug Dictionary
  • 44. SIDE EFFECTS OF BENZODIAZEPINES 44 • Headaches • Confusion • Ataxia (Disorders that affects coordination, balance and speech) • Dysarthria (Difficulty speaking) • Blurred vision • GI disturbances • Paradoxical excitement • Impair cognition (e.g., memory, attention and processing speed) 23 Crowe SF et al. The residual medium and long‐term cognitive effects of benzodiazepine use: an updated meta‐analysis. Arch Clin Neuropsychol 2017; doi: 10.1093/arclin/acx120. [Epub ahead of print]
  • 45. APPROPRIATE USE OF BENZODIAZEPINES ● Benzodiazepines provide rapid symptomatic relief from acute anxiety states. ● Only use for severe anxiety, disabling or in extreme distress. ● Use lowest effective dose + shortest time (max 4 weeks). ● Caution in patients with substance misuse. 45 Department of Health (DoH). Benzodiazepines: Good Practice Guidelines for Clinicians (2002).Accessed at www.health.gov.ie/wp-content/uploads/2014/04/Benzodiazepines-Good Practice-Guidelines.pdf on 14 February 2017.
  • 47. PHARMACIST’S ROLES ▰ There is so much that we can do to improve patient’s quality of life. ▰ It all begins with patient being able to adhere to medication. 47
  • 48. PHARMACIST’S ROLES ▰ Pharmacists have the potential to have a large effect in enhancing patient’s quality of life through a variety of interventions such as :1 ▻ reducing the number of medications taken ▻ reducing the number of doses taken, increasing patient adherence, ▻ preventing adverse drug reactions (ADRs), ▻ improving patient quality of life and ▻ decreasing facility and drug costs. 48 1. Chumney EC, Robinson LC. The effects of pharmacist interventions on patients with polypharmacy. Pharm Pract (Granada). 2006 Jul;4(3):103-9. PMID: 25247007; PMCID: PMC4156841.