11/25/2020

RECENT STRIDES IN PSYCHOPHARMACOLOGY: HELPING YOUR PATIENTS REACH THE FINISH LINE

MN NACNS PHARMACOLOGY SYMPOSIUM ELENA GEIGER-SIMPSON, DNP, APRN, PMHNP-BC, PHN

DISCLOSURE NO CONFLICTS OF INTEREST TO DISCLOSE

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The purpose of this presentation is to provide an overview of current trends and advances in psychopharmacology.

OBJECTIVES Learners will be able to indicate understanding of current pharmacological interventions used to treat a broad array of psychiatric conditions.

Mental Health Conditions • Depressive disorders • Anxiety disorders • • Obsessive and Compulsive Disorders PSYCHOPHARMACOLOGICAL USES • Bipolar disorder • Attention deficit-hyperactivity disorder • Substance use disorders • Post-traumatic stress disorder • And more…

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DRUG CLASSES Mood stabilizers

Antidepressants

Anxiolytics

Stimulants

Substance Use Disorder

ANTIPSYCHOTICS

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• Psychosis • Schizophrenia • Treatment Resistant Depression • Agitation/Anxiety INDICATIONS • Bipolar Disorder • Aggressive Behavior • Sleep

First Generation Typical CLASSES Second Generation (SGA) Atypical

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MECHANISM OF ACTION

Mesocortical Mesolimbic Tuberoinfundibular Nigrostriatal • 4 Pathways Worsening *Decrease Increase prolactin EPS cognition Positive Sx • Dopamine antagonists Increase Apathy Galactorrhea Tardive • Block action of dopamine on D2 negative sx Dyskinesia receptors • SGAs- dopamine and Low Amenorrhea antagonists motivation • Dopamine 2 partial agonists Anhedonia • Other receptor action: Muscarinic Decreased cholinergic, histaminergic, alpha 1- interest adrenergic

FIRST GENERATION OR TYPICAL

High Potency

• More EPS; fewer anticholinergic effects, orthostatic hypotension, and sedation

Low Potency

• Less EPS; more histaminergic and anticholinergic effects

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SECOND GENERATION (SGA) OF ATYPICAL

Same Effect on Lower EPS Increased Risk of More Effect on Positive Sx Metabolic Syndrome Negative Sx

ADVERSE REACTIONS MONITORING

• EPS • EKG for meds high risk for QTc prolongation • Anticholinergic Side Effects • AIMS or Discus • Lipid profile • Tardive Dyskinesia • Fasting blood glucose • Metabolic Syndrome • A1C • Neuroleptic Malignant Syndrome • Weight • Agranulocytosis (neutropenia) with Clozaril • Waist circumference • Liver panel • Prolactin Level • CBC

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• Improve negative symptoms and cognitive function. • Limit adverse effects. • transdermal system • NEW • /samidorphan ADVANCES • • in situ Microparticle (ISM) • • Trace Amine-Associated Receptor 1 (TAAR-1) Agonists

(Maroney, 2020)

PEARLS

• Consider • Outcomes • REASON for poor adherence • How to improve adherence • Remember • is just one piece

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MOOD STABILIZERS

• Bipolar Disorder • Acute Mania • Prophylaxis of mania/depression • Adjunctive • Aggression • Impulsivity INDICATIONS • Anxiety • Mood lability • Chronic Pain Syndromes • Schizoaffective Disorder

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Anticonvulsants

CLASSES Atypical Antipsychotics/SGAs

Lithium

• Lithium: cholinergic and GABA activity, dopamine receptor sensitivity, activity, inhibits second messenger system • Anticonvulsants: action on neurotransmitters NE, MECHANISM ACTH, DA, GABA, Glutamate; inactivation of OF ACTION voltage-dependent sodium channels • SGAs: D2 antagonism/partial agonist; 5HT2A antagonist and 5HT1A partial agonist; reduction of glutamate hyperactivity

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• Specific side effects largely depend on drug • Lithium toxicity: ataxia, slurred speech, tremor, N/V, tinnitus, blurred vision, Coma, seizures, and death above 2.5 mEq/L ADVERSE • Steven’s Johnson Syndrome:• Life threatening rash; higher incidence in children; most cases occur within 8 weeks of REACTIONS starting medication; systemic symptoms such as flu like, fever, malaise, pharyngitis, sores/blisters on soles/palms or mucus membranes • Pregnancy considerations: teratogenic- neural tube defects, spina bifida, craniofacial defects, decrease efficacy of OCT

Medications/Labs Recommendations Notes Lithium

Serum Level After 1 week then after dose changes, Levels will not change after they reach steady compliance issues, or new side effects state levels unless an outside factor intervenes

TSH Baseline, 2 weeks, 6 months, yearly Thyroid issues typically arise 2 weeks to 6 months after starting lithium

BUN/Creatinine Baseline Baseline, 2 weeks, yearly EKG Not needed for most patients unless over age of Small incidence of bradycardia due t sinus node 40 years old or those with cardiac history dysfunction- will require more than an EKG and will need specialty follow up

Valproic Acid (Depakote)

Serum Level After 1 week then after dose changes, Levels will not change after they reach steady compliance issues, or new side effects state levels unless an outside factor intervenes

LFTs Baseline, 2 weeks, yearly unless symptoms of hepatitis Hepatotoxicity rare, mild increased LFTs more common and usually benign and reversible

CBC After 2 weeks, 6 months, yearly (unless easy bruising or older adult) Thrombocytopenia is rare, but older adults are at higher risk Carbamazepine Serum Level After 1 week, one month, yearly or more often if Because of auto-induction, levels at 1 month are dose changes, compliance issues, or new side helpful, but no further induction expected after effects that time

CBC At 1 week, 1 month, 3 months, yearly Leukopenia is rare, but often occurs within 1 month Sodium and LFTs After 2 weeks, then yearly unless symptoms of hepatitis Actual hepatitis is rare

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NEW ADVANCES AND OTHER TREATMENTS

• CANMAT Guidelines • National trends for treatment of pediatric- onset bipolar disorder with second generation with evidence for efficacy and safety. (Olfson et al. Arch Gen Psychiatry (2006) 63:679- 685.)

• Calcium channel blockers • ( + olanzapine) • , • • Omega -3 Fatty acids, Inositol, L-methyl folate

• Thyroid hormone • ECT/TMS

(Yatham et al., 2018)

(Yatham et al., 2018)

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ANTIDEPRESSANTS

• Depression • Phobias • Obsessive-compulsive behaviors • Panic • Anxiety INDICATIONS • PTSD • Sleep • Trauma • Chronic Pain • Migraine Prophylaxis

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• Selective serotonin reuptake inhibitors (SSRIs) • Selective norepinephrine reuptake inhibitors (SNRIs) • Norepinephrine-dopamine reuptake inhibitors (NDRIs) • antidepressants (TCAs) CLASSES • Monoamine oxidase inhibitors (MAOIs) • Serotonin partial agonist/reuptake inhibitor (SPARIs) • Serotonin antagonist/reuptake inhibitor (SARIs) • Alpha-2 antagonist

MECHANISM OF ACTION

• SSRI: Block reuptake of 5HT in presynaptic nerve terminals, some SSRIs have higher affinity for DA and NE. • SNRI: Block reuptake of 5HT and NE, more beneficial for lethargy, fatigue-based sx • NDRI: Block • TCA: block reuptake of NE and 5HT in presynaptic nerve terminals • MAOI: block action of monoamine oxidase (slowing destruction of NE, DA, 5HT) • SPARI: serotonin partial agonist/reuptake inhibitor • SARI: Blocks 5HT 2A and receptors • Alpha-2 antagonist- enhance release of monoamines (5HT and NE) in cortex

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• Activation • Insomnia • GI • Sexual side effects • Weight Gain ADVERSE • Black box warning REACTIONS • Anticholinergic- TCAs and MAOI • Orthostatic hypotension • Risk of death via overdose: TCA and MAOI • Hypertensive crisis- MAOI and Tyramine • Serotonin Syndrome: too much serotonin in synaptic cleft; tremor, myoclonus, altered mental status, agitation, diarrhea, fever, diaphoresis, hyperreflexia, delirium, coma, death

LABS/MONITORING

• Screening in depression: CBC, electrolytes, BUN and Creatinine, LFTs, B12, Red blood cell folate level, TSH • Metabolic screening • Vital signs, orthostatic • ECG

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NEW ADVANCES

• TMS • Glutamatergic therapies • Ketamine/Esketamine • Atypicals • BDNF • Inflammation

(Gordon, 2019)

PEARLS

• Medication is only part of the puzzle • Psychotherapy • Nutrition • Exercise • Stress reduction • Behavioral activation • Cognitive-based approaches

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ANXIOLYTICS

This Photo by Unknown Author is licensed under CC BY-SA

INDICATIONS

• Anxiety • Panic • Nightmares • Decrease physiological arousal • PTSD • Agitation

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• Antidepressants • Benzodiazepines: short acting, intermediate-acting, long- CLASSES acting • Other agents/Off label uses: , gabapentin, , , prazosin, , pregabalin, clonidine

MECHANISM OF ACTION

• Serotonergic activity • GABA receptor agonists • Beta blockers: block effects of catecholamines • Alpha 2 Agonists: slow HR, decreases sympathetic nervous system response

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• MN PMP • Controlled substance agreement • Not for scheduled or long-term use BENZODIAZEPINE • Caution with withdrawal MONITORING • Taper • Gradual vs. long term • Adjunctive medications • Non-pharmacological interventions

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PEARLS

• Medication used to “turn down the volume” of anxiety • Address it head on– don’t keep pushing it down the road. • CBT, CBT, CBT and other types of therapy; exposure therapy; trauma focused • Motivational Interviewing • Exercise • Sleep • Reduce stimulants • Supplements

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STIMULANTS

This Photo by Unknown Author is licensed under CC BY-SA-NC

INDICATIONS

• ADHD • Obesity • Narcolepsy • Treatment-resistant depression • Cognitive impairment/neurobehavioral sx after TBI, stroke, dementia

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Methylphenidate Products Salt Products CLASSES

MECHANISM OF ACTION:

METHYLPHENIDATE This image cannot currently be displayed.

Blocks the reuptake Blocks the reuptake of Dopamine of Norepinephrine Increased availability Increased availability in the synapse in the synapse

(Stahl, 2013)

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MECHANISM OF ACTION: AMPHETAMINE SALTS

This image cannot currently be displayed. Competitive inhibitor of DAT Competitive inhibitor of NET Competitive inhibitor of VMAT

(Stahl, 2013)

ADVERSE REACTIONS MONITORING

This image cannot currently • Appetite • Dizziness be displayed. Visits every month until optimal response, then 3 months, then 6 months suppression • Palpitations

This image cannot currently be displayed. • Irritability • Euphoria Height, weight, heart rate, blood pressure

• Abdominal Pain This image cannot currently • Weight loss be displayed. Cardiac monitoring if indicated • Headache • Sudden death

This image cannot currently • Tics • Dependence be displayed. Dosage and timing of medications • Insomnia This image • Psychosis cannot currently be displayed. Comorbid issues (sleep problems, depression, substance use disorders, sexual activity, etc.)

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PEARLS

Multiple Studies Suggest: Children taking stimulants to treat ADHD do not develop dependence or signs of addiction. Children taking stimulants to treat their ADHD may REDUCE their risk for developing substance use disorders

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MEDICATIONS USED IN SUBSTANCE USE DISORDER

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• Substance Use Disorders INDICATIONS • Chronic pain • Opioid detoxification

MEDICATIONS

Naltrexone/Vivitrol Acamprosate Disulfiram Buprenorphine products Methadone

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MECHANISM OF ACTION

• Naltrexone: mu opioid receptor, reduces “high” • Disulfiram: irreversible inhibits aldehyde dehydrogenase causing severe reaction when is consumed • Acamprosate: reduces excitatory glutamate transmission, inhibits GABA transmission. • Methadone: full opioid agonist • Buprenorphine products: mu opioid , prevents biding of opioids; mu receptor partial agonist, prevents exogenous opioids from binding to receptor

ADVERSE REACTIONS

• Naltrexone: nausea/vomiting, dizziness, headache, anxiety, dysphoria, insomnia, Injection site reaction, hepatotoxicity (dose dependent) • *Must be free of opioids at least 7-10 days • Disulfiram: ingestion of alcohol- flushing, headache, tachycardia, nausea, and vomiting; dermatitis; metallic taste; sedation • Acamprosate: diarrhea, nausea, anxiety, dysphoria with possible SI • Methadone: respiratory depression, ECG changes, arrhythmia, syncope, hypotension, hallucinations, dizziness, confusion, euphoria, dependence, seizures, decreased libido, skin rashes, weight gain • Buprenorphine products: headache, orthostatic hypotension, nausea, constipation, sedation, respiratory depression, hepatotoxicity

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REMEMBER

• Substance Use Disorders are not a character flaw or lack of will power • MAT is an important component of treatment and recovery • There is a shortage of providers trained in using MAT

QUESTIONS?

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REFERENCES

• Gordon, J. (2019). New hope for treatment-resistant depression: Guessing right on ketamine. National Institute of Mental Health. https://www.nimh.nih.gov/about/director/messages/2019/new-hope-for-treatment-resistant-depression-guessing-right- on-ketamine.shtml • Maroney, M. (2020). An update on current treatment strategies and emerging agents for the management of schizophrenia. American Journal of Managed Care, 26(3), 55-61. https://doi.org/10.37765/ajmc.2020.43012 • Stahl, S. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical application (4th ed.). Cambridge University Press. • Yatham, L.N., Kennedy, S.H., Parikh, S.V., Schaffer, A., Bond, D.J., Frey, B.N., Sharma, V., Goldstein, B.I., Rej, S., Beaulieu, S., Alda, M., MacQueen, Gl., Miley, R.V., Ravindran, A., O’Donovan, C., McIntosh, D., Lam, R.W., Vazquez, G., Kapczinski, F…Berk, M. (2018). Canadian network for mood and anxiety treatments (CANMAT) and international society for bipolar disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disorders, 20, 97-170. DOI: 10.1111/bdi.12609

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