Simply Psych EDU © Handbook of Psychiatry

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Michael T Ingram Psychiatry Inc. 2021

2 Simply Psych EDU © Handbook of Psychiatry

HANDBOOK OF PSYCHIATRY

2021

Michael T. Ingram, M.D.

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CONTENTS

Psychiatric Evaluation ............................... 17

Components of the evaluation ............. 17

Mental Status Examination ....................... 19

Emergency Psychiatry ............................... 22

Acute Agitation ..................................... 22

Drugs of Abuse ...................................... 23

Urine Toxicology: .............................. 23

False Positives: .................................. 23

Alcohol .................................................. 24

Medical complications of chronic alcohol use ........................................ 24

Alcohol Withdrawal Timeline ............ 25

Alcoholic Hallucinosis: ....................... 25

Alcohol withdrawal syndrome: ......... 25



Alcohol withdrawal seizures: ............ 26

Alcohol withdrawal delirium (Delirium tremens): ........................................... 26

Wernicke Korsakoff Syndrome (WKS): .......................................................... 27

Alcohol Intoxication/Poisoning: ........ 27

Benzodiazepines for Alcohol Withdrawal ....................................... 28

Alcohol Withdrawal Treatment Table .......................................................... 28

Serotonin Syndrome & NMS ................. 29

Lithium Toxicity ..................................... 30

Catatonia ............................................... 31

Presentation: ..................................... 31

Causes: .............................................. 31

Treatment: ........................................ 31



Suicide Risk Assessment ........................ 32

RISK FACTORS .................................... 32

PROTECTIVE FACTORS ....................... 32

Risk FACTORS FOR VIOLENCE: ............... 33

Consultation Liaison Psychiatry ................ 34

Delirium|Altered Mental Status ........... 34

General Concepts: ............................. 34

Predisposing factors: ......................... 34

Precipitating factors: ......................... 35

Behavioral Management:.................. 35

Pharmacological Management: ........ 35

Physical restraints: ............................ 36

Geriatrics ............................................... 36

General Comments: .......................... 36

Delirium/Dementia Management: .... 37



Depression in the Elderly: ................. 37

Psychopharmacology in medically complex patients ..................................................... 38

Patients with Cardiovascular Disease 38

Patients with Liver Disease ............... 45

Patients with Renal Disease .............. 46

Patients with Respiratory Disease .... 47

Patients with Neurological Disease ... 48

Capacity ................................................. 50

Capacity Vs. Competence ................. 50

Criteria for Decision-Making Capacity .......................................................... 51

Documenting Capacity ...................... 51

Pregnancy & Post-Partum Period ......... 53

Inpatient Psychiatry .................................. 55

Treating common patient complaints:.. 55



Insomnia ........................................ 55

Break-through anxiety ................... 56

Pain ................................................ 56

Pruritus .......................................... 56

Akathisia ........................................ 56

Dystonic reactions ......................... 56

Parkinsonism .................................. 57

Tardive Dyskinesia ......................... 57

Psychopharmacology ................................ 58

Drug Schedules ..................................... 58

Terms & Definitions: ............................. 58

Drug Levels, Labs, & Monitoring ........... 60

Antipsychotics ....................................... 61

SIDE EFFECTS (LEAST TO MOST) ........ 61

Benzodiazepines ................................... 61



Benzodiazepine Equivalency Table: .. 64

Treating Extrapyramidal Symptoms ...... 64

Drug Interactions Table ......................... 65

High Yield Psychopharmacology concepts .................................................................. 67

General Concepts .................................. 67

Lithium .................................................. 71

Antidepressants .................................... 73

Antipsychotics ....................................... 76

Mood Stabilizers ................................... 79

Important Drug-Drug Interactions ............ 81

Valproic acid (VPA) + Lamotrigine: ........ 81

Carbamazepine (CBZ) is an inducer of CYP3A4 .................................................. 81



Lithium + NSAIDs (not aspirin), ACE Inhibitors, Thiazide diuretics, low sodium diet: ....................................................... 82

Lithium + caffeine, theophylline, high sodium diet: .......................................... 82

Grapefruit Juice ..................................... 82

Smoking Tobacco cigarettes: ................ 83

Tyramine ............................................... 83

Fluoxetine, Paroxetine, and Bupropion are potent inhibitors of CYP2D6 ........... 83

Antimicrobial-Psychotropic Drug Interactions: .......................................... 84

Other Interactions/Adverse Reactions: 84

Medication Quick Reference..................... 86

Fluoxetine (Prozac) ............................... 86

Sertraline (Zoloft) .................................. 88



Paroxetine (Paxil) .................................. 90

Fluvoxamine (Luvox) ............................. 92

Citalopram (Celexa) ............................... 94

Escitalopram (Lexapro) ......................... 96

Duloxetine (Cymbalta) .......................... 98

Venlafaxine (Effexor)........................... 100

Desvenlafaxine (Pristiq) ...................... 103

Levomilnacipran (Fetzima) .................. 105

Bupropion (Wellbutrin) ...................... 106

Mirtazapine (Remeron) ...................... 108

Trazodone (Desyrel) ........................... 110

Vortioxetine (Trintellix) ...................... 112

Tricyclic Antidepressants (TCAs) ......... 114

Buspirone (Buspar) ............................. 117

Gabapentin (Neurontin) ...................... 119



Pregabalin (Lyrica) ............................... 121

Lithium ................................................ 123

Valproic Acid (Depakote) .................... 126

Carbamazepine (Tegretol) .................. 129

Lamotrigine (Lamictal) ........................ 131

Topiramate (Topamax) ....................... 134

Methylphenidate (Ritalin, Concerta) .. 137

(D,L) Amphetamine (Adderall) ............ 140

(D) Amphetamine (Dexedrine) ............ 142

Lisdexamfetamine (Vyvanse) .............. 144

Typical Antipsychotics ......................... 147

Side Effects of Typical Antipsychotics ........................................................ 148

Receptors and side effects .............. 148

Atypical Antipsychotics ....................... 151



Side Effects of Atypical Antipsychotics ........................................................ 152

Clozapine (Clozaril).............................. 154

Risperidone (Risperdal) ....................... 156

Olanzapine (Zyprexa) .......................... 157

Quetiapine (Seroquel) ......................... 160

Aripiprazole (Abilify) ........................... 162

Ziprasidone (Geodon) ......................... 164

Asenapine (Saphris) ............................ 165

Lurasidone (Latuda) ............................ 167

DSM-5 Diagnostic Criteria ....................... 168

Psychotic Disorders ............................. 168

Schizophrenia .................................. 168

Schizophreniform Disorder ............. 170

Brief Psychotic Disorder .................. 171



Schizoaffective Disorder ................. 171

Delusional Disorder ......................... 172

Mood Disorders .................................. 174

Major Depressive Disorder ............. 174

Bipolar Disorder .............................. 176

Disrupted Mood Dysregulation Disorder (DMDD) ............................ 180

Persistent Depressive Disorder (Dysthymia) ..................................... 182

Premenstrual Dysphoria Disorder (PMDD) ............................................ 184

Anxiety Disorders ................................ 187

Generalized Anxiety Disorder ......... 188

Separation Anxiety Disorder ........... 189

Specific Phobia ................................ 191

Social Anxiety Disorder ................... 193



Panic Disorder ................................. 194

Panic Attack Specifier ...................... 196

Agoraphobia .................................... 196

OCD and Related Disorders ................. 198

Obsessive Compulsive Disorder ...... 198

Body Dysmorphic Disorder ............. 199

Hoarding Disorder ........................... 200

Hair Pulling Disorder (Trichotillomania) ........................................................ 200

Excoriation (Skin-Picking) Disorder . 200

Attention Deficit Hyperactivity Disorder (ADHD) ................................................ 201

Eating disorders .................................. 203

Bulimia Nervosa .............................. 203

Anorexia Nervosa ............................ 204

Post Traumatic Stress Disorder ........... 205



ICD-10 Codes ........................................... 209

Neurodevelopmental Disorders .......... 209

ADHD ................................................... 210

Somatic Symptom and Related Disorders ............................................................ 212

Psychotic Disorders ............................. 212

Bipolar Disorders ................................. 216

Dissociative Disorders ......................... 218

Feeding and Eating Disorders ............. 218

Depressive Disorders .......................... 220

Impulse-Control and Conduct Disorders ............................................................ 222

Medication Induced Movement Disorders and Other Adverse Effects of Medications ............................................................ 223

Anxiety, OCD, and Trauma Disorders .. 224



Substance Use Disorders..................... 229

References .............................................. 237



PSYCHIATRIC EVALUATION

COMPONENTS OF THE EVALUATION

Patient Identification Name, Age, Gender identity

Chief Complaint Reason for visit/admission

History of Present Illness

Symptom(s) onset, duration, severity, aggravating and alleviating factors, additional stressors.

Psychiatric Review of Symptoms

Depression (SIGECAPS)* Manic/Hypomanic Symptoms (DIGFAST)** Anxiety Symptoms Psychotic Symptoms

Substance Use History

Drug name(s), Date of first use, Quantity, Frequency, Duration, Longest period of sobriety (LPOS), Last use

Past Psychiatric History

Outpatient treatment history Inpatient treatment history Previous medication trials History of self-harm, suicide attempts, and violence

Past Medical History Medical problems, Past Surgeries, Medications, Allergies

Family History Psychiatric Disorders, Suicide attempts, completed suicide, substance use

Social History

Birthplace Early parental figures Developmental Milestones Education history

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Relationship History Marital status Social Support Religious preference Trauma and/or Abuse history Current Living Situation Employment History Legal History (arrests, DUIs, prison time)

Medical Review of Systems

Constitutional Skin HEENT Neck Cardiovascular Pulmonary Gastrointestinal Genitourinary Musculoskeletal Lymphatic Endocrine Neurological

Physical Examination

Mental Status Exam Neurological Exam Neurobehavioral Exam

*SIGECAPS: Sleep disturbances, lack of Interest, low Energy, Concentration

problems, Appetite changes, Psychomotor changes, Suicidal thoughts

**DIGFAST: Distractibility, Impulsivity, Grandiosity, Flight of Ideas, Agitation, lack

of Sleep, Talkative/pressured speech

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MENTAL STATUS EXAMINATION

VITAL SIGNS Temperature, Heart Rate, Blood Pressure, Respiratory Rate, Oxygen Saturation, Weight, Height

ALERTNESS/ORIENTATION Is the patient awake, alert, and oriented to person, place, time, date, situation? Is the patient drowsy, confused, sedated, or lethargic?

APPEARANCE Does the patient appear his or her age? Is the patient wearing appropriate attire? Is the patient disheveled? How is the patient’s hygiene? Are there any physical abnormalities or distinguishing features such as tattoos, hairstyle, scars, or unusually smells? How is the patient’s posture?

BEHAVIOR Is the patient cooperative? Does the patient make appropriate eye contact? Behavioral descriptors include guarded, evasive, angry, seductive, bored, distracted, disinterested, indifferent/apathetic, pleasant, preoccupied, sarcastic, passive-aggressive, hostile, threatening, crying, tearful, smiling, laughing (inappropriate laughing, giggling, smiling).

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MOTOR Is the patient’s motor activity slowed/decreased (e.g., parkinsonian, catatonic) or hyperactive/agitated/increased (e.g., restless, fidgety, chorea, pacing, foot tapping, hand wringing, skin picking)? Any abnormal movements present such as tics, dystonia, rigidity, tardive dyskinesia, athetoid, akathisia? Does the patient have a normal gait?

SPEECH How is the patient’s speech rate, rhythm, volume, quantity, articulation? Does the patient speak fluently and spontaneously?

MOOD How does the patient describe their mood state?

AFFECT How does the patient’s mood appear to you (i.e., affect is the outward expression of the patient’s emotional state)? Note the Stability, Range, Appropriateness, Intensity, and Quality (depressed, sad, happy, angry, euphoric, irritable, anxious, neutral, fearful, apathetic, pleasant)

THOUGHT CONTENT Does the patient have suicidal ideations (passive, active), homicidal ideations, depressive cognitions, obsessions, compulsions, ruminations, phobias, ideas of reference, paranoid ideation, magical ideation, delusions, overvalued ideas? Are there any recurrent major themes discussed by the patient?

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THOUGHT PROCESS Is the patient’s thought process linear, logical, and goal-directed or is it circumstantial, tangential, illogical, perseverative, and incoherent? Does the patient have disorganized thoughts, flight of ideas, loose associations, clang associations, neologisms, or thought blocking?

PERCEPTION Does the patient report Hallucinations, Illusions, Depersonalization, Derealization, Déjà vu, Jamais vu? Is the patient responding to internal stimuli?

INTELLECT Average, above average, below average?

INSIGHT Does the patient demonstrate adequate understanding of their illness and the current situation?

JUDGEMENT Does the patient have good judgement? Ask a question RELATED TO THE CURRENT SITUATION (e.g., hypothetical scenarios, etc.).

IMPULSE CONTROL Is the patient impulsive and unpredictable?



Diazepam has a rapid onset of action due to its rapid absorption and distribution (very lipid-soluble) Diazepam has a shorter duration of clinical action than

lorazepam after one dose Intramuscular administration of diazepam and

chlordiazepoxide have unreliable and unpredictable absorption Benzodiazepines are all positive allosteric modulators of the

GABA-A Receptor Benzodiazepines that preferentially bind to the α1 subunit of

the GABA-A receptor are thought to have more sedative/hypnotic effects while those that preferentially bind to the α2 and α3 subunits of the GABA-A receptor are thought to have anti-anxiety effects (but there is little evidence to support this at this time) Benzodiazepines increase the binding affinity of GABA for its

receptor and increase the frequency of opening of the chloride channel embedded within the GABA-A receptor. This leads to increased chloride influx and hyperpolarization

of the dendritic portion of neurons bearing GABA-A receptors). When benzodiazepines are given to an individual suffering

from acute stress disorder, the probability of conversion to PTSD is roughly doubled (i.e., benzodiazepines may interfere with post trauma adaptation). Exposure therapies for anxiety disorders and PTSD do not

work as well if performed in the presence of a benzodiazepines.



Short course of benzodiazepines are commonly prescribed when starting SSRIs/SNRIs in patients with high anxiety to minimize activating side effects that can occur when initiating these agents The following benzodiazepines have little, if any, phase 1

metabolism in the liver and primarily undergo glucuronidation (and therefore they are preferred for individuals with hepatic impairment): • Oxazepam • Temazepam • Lorazepam

Benzodiazepines have been associated with: • Tolerance, physical dependence, withdrawal • Abuse potential • Ataxia • Diminished attention • Failure of memory consolidation • Increased risk of falls in the elderly • Increased risk of delirium in the elderly



BENZODIAZEPINE EQUIVALENCY TABLE:

Dosage Equivalency (mg)

Elimination half-life (hrs)

Alprazolam (Xanax) 0.5 6-20 Chlordiazepoxide (Librium) 10 30-100 Clonazepam (Klonopin) 0.25 18-50 Diazepam (Valium) 5 30-100 Lorazepam (Ativan) 1 10-20 Midazolam (Versed) -- 2-3 Oxazepam (Serax) 15 8-12 Temazepam (Restoril) 30 8-20

TREATING EXTRAPYRAMIDAL SYMPTOMS

Side Effect Treatment Options Acute Akathisia Propranolol (30mg-90mg/day)

Benzodiazepines Diphenhydramine

Parkinsonism Reduce dose Benztropine 1-2mg/day

Tardive Dyskinesia Reduce dose Discontinue Ingrezza

Hyperprolactinemia (symptomatic)

Reduce dose Discontinue

Acute Dystonia Benztropine 1mg-2mg IM



DRUG INTERACTIONS TABLE

Substrates Inhibitor Inducer

1A2

Caffeine Theophyline TCAs Ropinirole Duloxetine Mirtazapine Clozapine Haloperidol Olanzapine Asenapine Tacrine Zolmitriptan

Fluvoxamine Fluoxetine Paroxetine Sertraline

Cimetidine Omeprazole Fluoroquinol. Ticlopidine

Phenobarbital Secobarbital Carbamazepine Phenytoin

Modafinil Tobacco Charcoal-grilled meat Rifampin

2C9

Warfarin Losartan NSAIDs Glipizide ARBs

Valproic acid Fluoxetine

Fluconazole Miconazole Amiodarone

Secobarbital Carbamazepine

Rifampin

2C19

BZDs PPIs SSRIs (citalopram) Amitriptyline

Fluvoxamine Fluoxetine

Ketoconazole Cimetidine Omeprazole Lansoprazole

Carbamazepine Valproic acid Phenobarbital Phenytoin

Rifampin



2D6

β-blockers Class 1C antiarrhythmics Codeine Amitriptyline Sertraline Haloperidol TCAs Risperidone Iloperidone Tramadol Venlafaxine Duloxetine Aripiprazole

Bupropion Fluoxetine Paroxetine Duloxetine Sertraline Citalopram Escitalopram Haloperidol Thioridazine

Terbinafine Quinidine Cimetidine Amiodarone Mibefradil Ritonavir

None None

3A4

Acetominophen BZDs Statins Macrolides Quinidine Indinavir, Ritonavir Amlodipine, Felodopine Diltiazem Atorvastatin Buspirone Sertraline Venlafaxine Mirtazapine Haloperidol Iloperidone Trazodone

Fluvoxamine Nefazodone

Clarithromycin Erythromycin Troleandomycin Fluconazole Ketoconazole Itraconazole Indinavir Cimetidine Verapamil Diltiazem

Carbamazepine Phenytoin Phenobarbital St. John’s Wort Morphine Nicotine Topiramate Felbamate

Rifampin Ritonavir Indinavir Efavirenz Pioglitazone Glucocorticoids



UGT

FGAs SGAs TCAs NSAIDs Carvedilol Furosemide Morphine Tramadol Lorazepam Oxazepam

Diclofenac NSAIDs Probenecid Valproic acid

Carbamazepine Phenytoin Phenobarbital Lamotrigine

Rifampin Carbapenems

HIGH YI ELD PS YCH OPH ARM AC OLO GY CO NC EPT S

GENERAL CONCEPTS

1) Elderly patients in general require lower doses of medications due to normal changes in total body water (TBW), muscle mass, fat %, and kidney/liver function associated with aging.

2) In patients with hepatic impairment, adjust dose by calculating the Child-Pugh Score (see above).

3) AST, ALT, and Alkaline Phosphatase are not reliable indicators of hepatic function.

4) Young men with increased muscle mass who abuse stimulants (methamphetamine) might be at higher risk for extrapyramidal symptoms after administering high potency antipsychotics (Minimal empirical evidence supporting this, but mainly anecdotal support)

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5) Seasonal Affective Disorder (SAD) can be treated with light therapy. Bupropion is also effective.

6) Avoid beta blockers, if possible, in patients with COPD or asthma

7) Oxazepam, Temazepam, and Lorazepam are typically used in patients with hepatic impairment as they do not undergo Phase 1 metabolism and primarily undergo glucuronidation. (“Outside The Liver”)

8) Zolpidem (Ambien) and Zaleplon can case dissociative-like state (sleep walking, binge eating, aggressive outbursts, night driving) and the patient will not remember doing any of those things

9) Restless Leg Syndrome: Replete iron if deficient. 1st line treatment are dopamine agonists (levodopa, ropinirole, pramipexole, rotigotine); Alternatives are benzodiazepines (clonazepam), gabapentin, anticonvulsants, opioids.

10) In patients who are overweight, obese, or who have a large neck circumference: Think Obstructive Sleep Apnea (OSA) if presents with excessive daytime sleepiness, fatigue, irritability, or memory problems. Order a sleep study.

11) Stimulants (Amphetamines, Methylphenidate), non-stimulants (atomoxetine, a norepinephrine reuptake inhibitor), and modafinil are used to treat ADHD and narcolepsy

12) Stimulants can be used in terminally ill elderly patients with depression and/or demoralization syndrome.

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13) Stimulants in children/adolescents: side effects include insomnia, anorexia, and tics

14) Remelteon is a good for initial insomnia due to short half life.

15) Benzodiazepine overdose treated with flumazenil (may precipitate seizures in those with pre-existing seizure disorders)

16) Naloxone (Narcan) is used for opioid overdose. Has a short half life so must give in intervals or patient may revert back to opioid/opiate induced coma/respiratory depression.

17) Anticholinergic agents (benztropine, atropine, diphenhydramine, doxepin, low-potency antipsychotics) can cause cognitive impairment, worsen dementia, and precipitate delirium in the elderly.

18) Electroconvulsive therapy (ECT) is has shown efficacy for severe refractory depression, depression during pregnancy, psychosis, mania, catatonia, malignant catatonia, and treatment refractory NMS

19) There are no absolute contraindications to ECT. Avoid ECT in patients with intracranial masses (due to increased intracranial pressure and risk of herniation). ECT alters cerebral hemodynamics.

20) Ethanol is broken down to acetaldehyde by alcohol dehydrogenase. Acetaldehyde is broke down to Acetyl CoA by acetaldehyde dehydrogenase. Disulfiram inhibits acetaldehyde dehydrogenase causing accumulation of acetaldehyde (facial flushing, nausea, vomiting, etc.). These reactions can occur with over the counter cough

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syrups or anything with alcohol in it. It is most effective for motivated patients with a good support system.

21) Narcolepsy (sudden REM sleep with loss of muscle tone/cataplexy) is diagnosed by Multiple Sleep Latency Test and treated with stimulants or modafinil.

22) Steady state of oral drugs is usually reached after 4-5 half-lives (Example: Li takes ~5 days to reach steady state after initiation or dose change)

23) Chronic alcoholic patients should always receive parenteral thiamine before administering glucose/dextrose

24) Treatment of Catatonia: Benzodiazepines (IV lorazepam first line) or ECT

25) ECT side effects: musculoskeletal pain, amnesia, headache

26) Seizures: Potential culprits are clozapine, chlorpromazine, clomipramine, bupropion, lithium (toxicity), abrupt withdrawal from benzodiazepines or anticonvulsants. Flumazenil also reduces seizure threshold.

27) Therapeutic Index (TI) = TD50/ED50

28) Propranolol (Inderal) is effective for social phobia (public speaking), akathisia, and essential tremor

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LITHIUM

1) Lithium is toxic to the thyroid gland

2) 5-10% of patients on lithium develop hypothyroidism, >30% of lifetime lithium patients have elevated TSH

3) Check TSH levels prior to starting lithium, at 6 months, then annually

4) Lithium Toxicity: Emergency dialysis indicated with symptoms of toxicity (tremors, ataxia, slurred speech, AMS) and Lithium levels > 2.5

5) Lithium is not protein bound and therefore is easily dialyzed.

6) Dialysis is not a contraindication for using lithium. Dose lithium immediately after dialysis only.

7) Lithium worsens skins conditions such as Acne and Psoriasis

8) Lithium’s mechanism of action is incompletely understood but thought to interact with signal transduction pathways (e.g., IP3 pathway)

9) Lithium and ECT: Lithium dose should be reduced or discontinued in patients undergoing ECT (may cause prolonged seizures)

10) Lithium use during pregnancy (especially 1st trimester) increases risk of Epstein’s anomaly (congenital downward displacement of tricuspid valve into the right ventricle)

11) Lithium level normal range is 0.6-1.2 (for acute mania target should be 1.0-1.5)



12) Decreased lithium levels with: Theophylline, caffeine, osmotic diuretics, acetazolamide, increased sodium intake

13) Increased lithium levels with: Na depletion, Diuretics, NSAIDs (not aspirin), COX-2 inhibitors, Tetracycline, ACE inhibitors

14) Lithium is also known to be a potential precipitant of serotonin syndrome in people concurrently on serotonergic medications such as antidepressants, buspirone, and certain opioids such as pethidine (meperidine), tramadol, oxycodone, fentanyl and others.

15) Lithium co-treatment is also a risk factor for neuroleptic malignant syndrome in people on antipsychotics and other anti-dopaminergic medications.

16) Lithium causes acquire nephrogenic diabetes insipidus in about 50% of patients on long term Lithium treatment

17) Lithium treatment and EKG changes: T-wave flattening or inversion

18) Lithium interferes with AV conduction and the pace making activity of the sinus node (avoid in sick sinus syndrome). Also avoid in Brugada syndrome (genetic defect of cardiac sodium channels)



ANTIDEPRESSANTS

1) In Elderly patients with depression or anxiety: Use SSRIs due to minimal side effects.

2) In Elderly patients with depression or anxiety: Avoid tricyclic antidepressants (TCAs), if possible, due to anticholinergic side effects (constipation, urinary retention, cognitive impairment, delirium risk), cardiovascular side effects, cognitive impairment, and orthostatic hypotension)

3) Selective Serotonin Reuptake Inhibitors (SSRIs) are first linetreatments for Obsessive Compulsive Disorder but usually require higher doses than would be prescribed for depression.

4) Clomipramine is most serotonergic of the Tricyclic Antidepressants (TCAs) and therefore is a good choice for SSRI-refractory Obsessive Compulsive Disorder.

5) All SSRIs, except maybe paroxetine, are very safe to use during pregnancy. Sertraline and Fluoxetine are the best first choices for pregnant patients as these have the most data for safety.

6) Paroxetine and Sertraline are minimally secreted in breastmilk and are the best choices for individuals who arebreastfeeding

7) SSRIs and the reported risk of persistent pulmonary hypertension of the newborn during 2nd and 3rd trimestersis controversial.

8) Safest SSRIs during pregnancy: Sertraline, Fluoxetine, Citalopram



9) Safest SSRIs during breast feeding: Paroxetine, Sertraline, Fluoxetine, Citalopram

10) Paroxetine is not a the best first choice as an antidepressant and anxiolytic during pregnancy due to a small risk of congenital defects

11) Paroxetine should be dosed once daily at bedtime due to anticholinergic and antihistamine properties (usually sedating)

12) Fluoxetine and Sertraline are generally considered more “activating” SSRI antidepressants (but not always).

13) Paroxetine does not have an active metabolite and has a relatively short half-life and therefore often causes withdrawal syndrome when abruptly stopped.

14) Paroxetine has anticholinergic properties and a potent inhibitor of CYP2D6

15) Sertraline (Zoloft) is a weight neutral SSRI

16) SSRIs have shown effectiveness in premenstrual dysphoria and irritability. Also for “hot flashes” in perimenopause.

17) Bupropion is a good choice for patients who smoke or have low libido.

18) Bupropion is a good choice for SSRI induced sexual side effects.

19) Bupropion is a good choice for seasonal affective disorder.

20) Bupropion should be used with caution in patient’s with a history of seizure disorders and/or eating disorders (appears to lower the seizure threshold)



21) Bupropion is the least likely of the studied antidepressantsto induce mania or cause rapid cycling in depressed patients with bipolar disorder

22) TCAs cause slowing of cardiac conduction leading to awidening of the QRS complex and fatal heart blocks.

23) Antidepressants with noradrenergic properties may be thebest choice for patients with depression and neuropathic pain.

24) SNRIs be dosed in the morning as they can cause insomniaif dosed too late in the day (but not always).

25) For patients with TCA overdose, the treatment of choice isNaHCO3 (sodium bicarbonate)

26) Monoamine Oxidase Inhibitors (MAOIs) carry a risk for hypertensive crises when used in combination with tyramine rich foods (aged cheese, red wine, deli meats, sausage, sauerkraut) as well as other catecholaminergic drugs (ephedrine, pseudoephedrine, amphetamines, and other monoamine antidepressants).

27) A discontinuation syndrome occurs most frequently with Paroxetine, Sertraline, duloxetine, and venlafaxine when abruptly stopped.

28) Fluoxetine is rarely associated with a discontinuation syndrome due to its very long half-life (fluoxetine is oftenused for SSRI discontinuation syndrome).

29) Trazodone: Risk of priapism “traza-BONE”

30) Trazodone has minimal anticholinergic activity and is a good choice for elderly patients (but there is a risk for falls due to

SAMPLESAMPLE



alpha 1 antagonism and associated orthostatic hypotension)

31) In patients with Bipolar Depression: Best choices are Lithium, Quetipaine, Olanzapine-Fluoxetine combination,Lurasidone, Lamotrigine, or Aripiprazole.

32) Before increasing the dose of antidepressants, ensure that the antidepressant treatment has been administered for a sufficient duration and at a sufficient dose. At least four (4) weeks are needed before it can be concluded that a patient is partially responsive or unresponsive to a specific intervention. No treatment should continue unmodified if there has been no symptomatic improvement after four (4) weeks.

33) Serotonin Syndrome: Seen with TCAs, MAOIs, SSRIs, SNRIs, Triptans, Linezolid, Methylene blue, meperidine, tramadol, dextromethorphan, fentanyl, St johns wort, MDMA

ANTIPSYCHOTICS

1) Clozapine ANC Monitoring: Weekly for 6 months, then biweekly for 6 months then monthly after 12 months

2) Neuroleptic Malignant Syndrome (NMS): Patient starts typical or atypical antipsychotic then develops delirium, fever, muscle rigidity, and extremely elevated CPK.

3) NMS can be caused by antipsychotics, phenothiazine antiemetics (promethazine, prochlorperazine), metoclopramide, or abrupt discontinuation of L-dopa.



4) NMS Treatment: Stop antipsychotic and administer intravenous fluids (IVF). Also, use cooling blankets, dantrolene, and/or bromocriptine if needed

5) Antipsychotics increase risk of extrapyramidal symptoms (EPS). Typical antipsychotics are associated with higher risk compared to atypical antipsychotics.

6) EPS includes Acute Dystonia, Pseudoparkinsonism, Akathisia, and Tardive Dyskinesia.

7) Acute dystonia (painful muscle spasms and contractions) can be lethal if laryngeal muscles involved.

8) Treatment of acute dystonia: Intramuscular benztropine (Cogentin) or diphenhydramine (benadryl)

9) Tardive dyskinesia: Repetitive, involuntary movements of the limbs, torso, and fingers. Grimacing, tongue movements, lip smacking, lip puckering, pursing of lips, excessive eye blinking

10) Treatment of Tardive Dyskinesia: Decrease dose or stop the offending agent. Try one of the new treatments available. If this is not possible, try clozapine.

11) Akathisia: Restlessness, can’t sit still, feel like they always need to be moving, rocking back and forth in chair.

12) Treatment of Akathisia: Propranolol.

13) Clozapine and Olanzapine are the most likely to cause metabolic syndrome (insulin resistance, glucose abnormalities, dyslipidemia), worsen diabetes, or even precipitate diabetic ketoacidosis.



SIDE EFFECTS: Peripheral Edema, Dizziness, Fatigue, Ataxia, Weight Gain RARE SIDE EFFECTS: Hypersensitivity skin reactions, angioedema, rhabdomyolysis NOTABLE INTERACTIONS: Reduced absorption with antacids; Additive sedative effects when used with other sedating medications PREGNANCY: More safety data needed BREASTFEEDING: More safety data needed FDA INDICATIONS: 1) Diabetic Peripheral Neuropathy 2) Neuropathic Pain 3) Post-herpetic neuralgia 4) Partial Seizures 5) Fibromyalgia Off label: Generalized Anxiety Disorder, Alcohol withdrawal, Benzodiazepine withdrawal, cannabis use disorder, and restless leg syndrome ADDITIONAL INFORMATION: • Pregabalin is structurally similar to Gabapentin but more

potent with greater bioavailability. • Pregabalin is a schedule V controlled substance due to

potential for abuse/dependence (abrupt withdrawal can cause insomnia, nausea, diarrhea, headache)



LITHIUM

HALF-LIFE: 18-24 hours INITIAL DOSE: 300mg-600mg PO per day (divided doses) TARGET DOSING RANGE: 600mg-1,200mg per day (Target level 0.8-1.0 mEq/L) BEST TIME TO DOSE: Any HOW TO DOSE: Initial 300mg-600mg at bedtime or divided in two doses. Gradually increase dose to target serum level of 0.6-1.0 mEq/L. Max dose is generally 2,400mg/day. SIDE EFFECTS: Nausea, diarrhea, upset stomach, frequent urination, increased thirst, tremors, headache, fatigue, lethargy, emotional blunting/flatness, Increased white blood cell count PREGNANCY: Avoid if possible (but not a contraindication) – Risk of Epstein Anomaly (cardiac defect) BREASTFEEDING: Avoid if possible (but not a contraindication)



FDA INDICATIONS: 1) Acute mania 2) Bipolar Disorder Maintenance in children and adults LITHIUM’S INTERACTIONS WITH THE BRAIN ARE COMPLEX AND INCLUDE: Desensitizing presynaptic 5ht-1a auto receptors in the

raphe nuclei and thereby increasing serotonin release Decoupling g-protein linked production of second

messengers Directly increasing transcription of fast response genes

(e.g. Kreb, phos, and jun) PROPOSED MECHANISMS OF ACTION OF LITHIUM: Alters sodium transport in myocytes/neurons Alters metabolism of catecholamines (da, ne,

epinephrine) Alters intracellular signaling via second messengers

(ip3 and pkc pathways) ADDITIONAL INFORMATION: • Lithium is a cation metal first used in the 19th century to

treat gout and discovered by John Cade in 1949 to exert anti-manic effects

• Lithium does not undergo metabolism and is not protein bound. It is cleared via the kidneys.

• Benign leukocytosis is common due to demarginalization of WBCs

• Despite being highly effective, lithium is not widely used due to its narrow therapeutic index. Optimal plasma concentrations for treatment of bipolar mood disorder are 0.8 to 1.2 meq/L, however, toxic signs and symptoms may begin at concentrations as low as 1.5 meq/L and serious



toxicity with risk of permanent neurological injury may occur at concentrations as low as 2.0 meq/L.

• Lithium may worsen skin conditions such as acne and psoriasis

• Lithium use during the first trimester of pregnancy may be associated with an increased risk of Epstein’s anomaly (downward displacement of tricuspid valve into a malfunctioning right ventricle) although this is controversial. Note that lithium has been safely used in pregnancy in select patients.

• Lithium is easily dialyzed and can be administered to patients on hemodialysis (Give dose after dialysis treatment)

• Caffeine may decrease lithium levels • Lithium + Haloperidol may increase the risk of NMS and

delirium • Lithium may cause abnormal involuntary movements • Lithium may increase the risk of serotonin syndrome if

administered with serotonergic agents • An increase or decrease of 300mg/day changes serum Li

levels approximately 0.25 mEq/L (rough estimate) • Effective for chronic suicidal thoughts in bipolar and

unipolar depression • Effective for aggressive and violent behaviors • Increased risk of nephrogenic diabetes insipidus (usually

reversible) – may be reduced with once daily dosing • Propranolol is an effective treatment for tremors associated

with lithium • Bradycardia, cardiac arrhythmia, sinus node dysfunction

may be seen with lithium therapy



VALPROIC ACID (DEPAKOTE)

HALF-LIFE: 9-16 hours STARTING DOSE: 250mg-500mg per day TARGET DOSING RANGE: 1000mg-1500mg PO daily BEST TIME TO DOSE: Bedtime (for Extended release) HOW TO DOSE: Initial 250mg-500mg PO QHS. Increase rapidly to effective dose. Alternatively: Initial 15-20 mg/kg/day (twice daily dosing). Target range 1000mg-1500mg daily. Target serum level: 50mcg/mL – 125mcg/mL. Max dose generally 4000mg/day SIDE EFFECTS: Sedation, Tremor, Dizziness, Ataxia, Asthenia (muscle weakness), Headache, Abdominal Pain, Nausea, Vomiting, Weight gain, Alopecia PREGNANCY: Avoid due to Neural Tube Defects



PREGNANCY RISKS: Neural tube defects (spina bifida, anencephaly, etc), Low IQ, Developmental delay

NOTE: Valproic should not be used during pregnancy except in special cases (consult a perinatal psychiatrist). There is little evidence that folate supplementation prevents or protects against neural tube defects (but it has not been shown to be harmful so not a bad idea to use)

BREASTFEEDING: Avoid

FDA INDICATIONS: 1) Seizures2) Acute Mania associated with Bipolar Disorder 3) Migraine prophylaxis

MECHANISM(S) OF ACTION: • Blocks voltage sensitive sodium channels• Increases brain concentrations of GABA • Unlike many other medications, lithium and the

antiepileptics alter brain signal transduction by dampening axonal signal transmission and by inhibiting cellular response to excitatory signals. Part of this is mediated by partial blockade of voltage-dependent sodium channels. This property alone is not sufficient as anti-epileptics which DO NOT show benefit in bipolar illness also exhibit inhibitory effects at voltage-dependent sodium channels.

• To date, the property best correlated with prophylaxis of mood cycling has been depletion of the second-messenger,triphosphoinositol (IP3).

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• Another candidate mechanism is increased guanine synthase kinase, type 3, activity. This enzyme plays a role in modulating both voltage and ligand-gated sodium channels.

LABS TO OBTAIN BEFORE STARTING VALPROIC ACID: Pregnancy test, Liver function tests, Platelet count

ADDITIONAL INFORMATION: • Valproic acid (Valproate) is considered an anticonvulsant

with mood stabilizing properties• Use of anticonvulsants in mood disorders developed out of

research looking at the effects of anticonvulsants on seizureactivity and the process of “kindling” in mice (i.e., repeatedly inducing seizures via electrical stimulation results in seizure activity even in the absence of any stimulation).

• Valproic acid (Depakote) was found to be superior to lithium in type II bipolar illness and in rapid cycling illness (but anticonvulsants and lithium together showed additivebenefits)

• In manic patients, plasma levels greater than 45 ug/mL may be required for antimanic effects (levels up to 100-125 ug/mL are often tolerated in manic patients)

• There is no consensus on the therapeutic plasma level range for valproic acid but likely between 50-100 ug/mL

• Valproate inhibits Lamotrigine metabolism• Combination of valproate and lamotrigine increases

lamotrigine levels and increases risk of rash and SJS/TEN• The dose of lamotrigine must be decreased by half the

normal dose when given in combination with valproic acid (valproic acid inhibits lamotrigine metabolism).

• Valproic acid associated with dose-relatedthrombocytopenia in ~24% of patients

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• Commonly associated with elevated liver enzymes • Valproic acid has been associated with encephalopathy,

specifically from elevated ammonia levels • Valproic acid + Topiramate increases risk of encephalopathy • Valproic acid metabolized primarily by liver but by

NonCYP450 enzymes • Valproic acid associated with Polycystic Ovarian Syndrome

(10% of women) • Valproic acid has been shown to be effective in neuropathic

pain

CARBAMAZEPINE (TEGRETOL)

HALF-LIFE: Initially 25-65 hours, then 15 hours after 2-4 weeks STARTING DOSE: 200mg PO BID TARGET DOSING RANGE: 400mg-600mg PO BID BEST TIME TO DOSE: Any



HOW TO DOSE: Initial 200mg PO BID. Increase by 200mg/d every 3-4 days to target dose. Max dose 800mg PO BID NOTABLE SIDE EFFECTS: Sedation, Fatigue, Nausea, Dizziness, Ataxia, Diplopia, muscle incoordination, nystagmus, Leukopenia, Thrombocytopenia, Rare Aplastic Anemia (fever, fatigue, pallor, bleeding gums), Risk of Aplastic Anemia increased by coadministration with clozapine, Rare Agranulocytosis, Rash (increased risk of SJ/TEN in Asians with HLA-B1502 allele (recommend testing for this allele prior to prescribing carbamazepine to individuals of Asian descent), Syndrome of Inappropriate ADH (Hyponatremia), Very rare hepatotoxicity, Cardiac arrythmias (slows cardiac conduction), Elevated GGT (not concerning unless >3x normal limit). PREGNANCY: AVOID BREASTFEEDING: AVOID FDA INDICATIONS: 1) Seizures 2) Trigeminal Neuralgia 3) Acute mania associated with Bipolar Disorder (Equetro) MECHANISM(S) OF ACTION: Blocks voltage sensitive sodium channels DRUGS THAT INCREASE CARBAMZEPINE LEVELS: Cimetidine, Ciprofloxacin, Diltiazem, Fluoxetine, Fluvoxamine, Doxycycline, Erythromycin (and other macrolide antibiotics), Fluconazole, Grapefruit juice, Isoniazid (INH), Ketoconazole, TCAs, Valproate, Warfarin, Norfloxacin, Verapamil



DRUGS WHOSE BLOOD LEVELS ARE DECREASED BY CARBAMAZEPINE: Atypical antipsychotics (olanzapine, risperidone, clozapine), Benzodiazepines, Doxycycline, Ethosuximide, Fentanyl, Glucocorticoids, Haloperidol, Methadone, Oral contraceptives, Phenothiazines, Phenytoin, Sertraline, TCAs, Theophylline ADDITIONAL INFORMATION: • Reports of CNS toxicity (dizziness, diplopia) associated with

combination of carbamazepine and lamotrigine • Metabolized primarily by CYP3A4 and also induces its own

metabolism by inducing CYP3A4 • Induces multiple other CYP450 isozymes as well as P-

Glycoprotein • May test positive (false positive) for tricyclics (TCAs)

LAMOTRIGINE (LAMICTAL)

HALF-LIFE: 25-33 hours With valproic acid: 48-70 hours With Carbamazepine: 13-14 hours STARTING DOSE: 25mg PO daily



TARGET DOSING RANGE: 50mg-200mg per day BEST TIME TO DOSE: Any (causes insomnia in some patients) HOW TO DOSE:

If dosing without valproic acid: >Initial 25mg PO Daily for two weeks >Increase to 25mg PO BID for two weeks >Increase to 50mg PO BID for two weeks >If tolerated, can consolidate to once daily dosing >Max dose without valproate typically 200mg per day If dosing with valproic acid: >Initial 25mg PO every other day for two weeks >Increase to 25mg PO daily for two weeks then 50mg PO daily >Max dose with valproate typically 100mg per day *RESTART TITRATION IF STOPPED/MISSED FOR >5 HALF LIVES*

SIDE EFFECTS: Rash (benign), Steven-Johnson’s Syndrome/TEN, Fatigue, Insomnia, vivid dreams, headache, nausea, upset stomach, diarrhea, hyponatremia, DRESS Syndrome PREGNANCY: Minimal data on safety in humans. Must weigh risk of discontinuing vs risk of teratogenicity (which is low) BREASTFEEDING: Minimal data on safety in humans. Recommend bottle/formula feeding



FDA INDICATIONS: 1) Bipolar Disorder (maintenance/preventing mood episodes) 2) Seizures in adults and children

ADDITIONAL INFORMATION: • Lamotrigine shows prophylactic and antidepressant

properties, but is no better than placebo in treating mania• Lamotrigine has been shown to reduce glutamate release

and modulate reuptake of monoamines including serotonin and dopamine

• Lamotrigine has been shown to increase the time betweenboth depressive and manic episodes

• May be a good add-on medication with lithium for bipolar depression

• Mostly case reports and open labeled trials support lamotrigine in rapid cycling bipolar disorder, bipolar depression, and mixed episodes but RCTs have not consistently demonstrated efficacy for these conditions

• Lamotrigine carries a risk of both benign rash and Steven Johnson’s Syndrome/TEN

• Rash associated with rapid dose escalation• Reduce dose and slow titration if benign rash develops • Interaction between valproic acid and lamotrigine: Valproic

acid inhibits lamotrigine metabolism; dose of lamotrigine must be decreased by half the normal dose when given in combination with valproic acid

• Many hormonal contraceptives decrease lamotrigine levels– Caution during contraceptive-free “pill-free” periods aslamotrigine levels may rise substantially. Conversely, lamotrigine may decrease levels of hormonal contraceptives

• Carbamazepine decreases lamotrigine levels

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• If lamotrigine stopped/missed for >5 half-lives then strongly consider restarting titration

TOPIRAMATE (TOPAMAX)

HALF-LIFE: 19-25 hours

STARTING DOSE: 12.5mg-25mg per day

TARGET DOSING RANGE: 50mg-200mg per day BEST TIME TO DOSE: Any

HOW TO DOSE: Initial 12.5mg-25mg per day. Increase dose by 25mg per week. Max dose usually 400mg/day. For weight loss/prevent weight gain: 50mg-150mg/day For Mood effects: 100mg-200mg per day in divided doses

SAMPLE



SIDE EFFECTS: Psychomotor slowing, Decreased concentration, Somnolence, Fatigue, Anorexia, Kidney stone

formation, cognitive side effects (“dope-a-max” or topamax “fog”) is a common reason for discontinuing PREGNANCY: Minimal data on safety. BREASTFEEDING: Minimal date on safety. FDA INDICATIONS: 1) Epilepsy 2) Prophylaxis of Migraine headaches Off Label: Antipsychotic-induced weight gain (usually 50mg-150mg daily), Neuropathic pain, Borderline personality disorder, Alcohol use disorders, Cocaine use disorders MECHANISM(S) OF ACTION: Blocks voltage sensitive sodium channels Inhibits glutamate release Potentiates activity of GABA Blocks calcium channels Topiramate inhibits carbonic anhydrase (increased risk of

metabolic acidosis and kidney stones) Topiramate may have prophylactic properties, but

appears to exert little benefit during acute bipolar depression or mania.

ADDITIONAL INFORMATION: • Used in children with Lennox-Gastaut Syndrome • Carbamazepine increases elimination of topiramate • Topiramate may increase plasma levels of phenytoin



• Topiramate is a weak inhibitor of CYP219 • Topiramate is weak inducer of CYP3A4

• Alcohol enhances sedation and may increase risk of seizures



METHYLPHENIDATE (RITALIN, CONCERTA)

*IR (INSTANT RELEASE) | XR (EXTENDED RELEASE)

Generic Name Brand Name Usual Starting Dose

Typical Daily Dose Range

Long-acting MPH Ritalin SR 20mg QAM 10-140mg

Ritalin LA 20mg QAM 20-120mg

Concerta 18mg QAM 18-144mg

Metadate CD 10-20mgQAM

10-120mg

Short-acting MPH Methylphenidate 10mg q4hrs 10-140mg

Methylin 10mg q4hrs 10-140mg

Ritalin 10mg q4hrs 10-140mg

D-methylphenidate Focalin 5mg q4-6hrs

10-80mg

Focalin XR 5-10mg QAM

10-80mg

MPH, Methylphenidate; XR, Extended Release; SR, Sustained Release; LA, Long-Acting

HALF-LIFE: 2-4 hours

TIME TO EFFECT: IR ~15-30min | Concerta/LA/SR ~1-2 hours

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PEAK IN PLASMA: IR 1-2 hours | Concerta/LA/SR ~5-8 hours

DURATION OF CLINICAL ACTION: IR 4-5 hours |Concerta/LA/SR ~ 8-12 hours

METABOLISM: Primarily Liver and Gut

WITH/WITHOUT FOOD: Methylphenidate is absorbed at a faster rate in the presence of food

BEST TIME TO DOSE: Morning

HOW TO DOSE: (See Table Above)

SIDE EFFECTS: Insomnia, Headache, Anxiety/Nervousness, Abdominal Pain, Anorexia, Nausea, Vomiting, Dry Mouth, Weight loss, Seizures (rarely with PO), Psychosis (rarely with PO), Elevated Blood Pressure, Tachycardia, Sudden death has been reported in patients with preexisting cardiac structural abnormalities

PREGNANCY: Avoid if possible (discuss with a medical professional)

BREASTFEEDING: Avoid if possible (discuss with a medical professional)

DRUG INTERACTIONS: Desipramine should be used with extreme caution if used with methylphenidate. Antacids increase absorption of methylphenidate. Dopamine antagonists such as haloperidol and chlorpromazine as well as lithium may inhibit stimulant effects. Avoid using with



monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crises and malignant hyperthermia

FDA INDICATIONS: 1) Attention deficit hyperactivity disorder in children andadults 2) Narcolepsy (R139italin, Concerta, 139Ritalin-sr,R139italin-la)

Off label: chronic fatigue, fibromyalgia, cognitive/memory problems

ADDITIONAL INFORMATION:

• Methylphenidate has four (4) possible stereoisomers because it has two (2) stereoactive centers. Dexmethylphenidate (brand name Focalin) is the most biologically active form and also 2x more potent than methylphenidate. Methylphenidates generally have fewer adverse effects compared to amphetamines. Methylphenidate was synthesized by CIBA (now Novartis) pharmaceuticals by chemist Leandro Panizzon, whose wife, Rita, used it for her chronic low blood pressure. Leandro named the drug “Ritaline” after hiswife.



(D,L) AMPHETAMINE (ADDERALL)

*IR (INSTANT RELEASE) | XR (EXTENDED RELEASE) HALF-LIFE: 9-14 hours TIME TO EFFECT: IR ~1 hour | XR ~1-2 hours PEAK IN PLASMA: IR 3 hours | XR 7 hours DURATION OF CLINICAL ACTION: IR 6-9 hours | XR 6-10 hours WITH/WITHOUT FOOD (PO): Taking with food may delay peak actions. pH of food alters absorption and elimination of amphetamines. GI and urinary Acidifying agents decrease plasma levels of amphetamines. GI and urinary alkalinizing agents increase plasma levels of amphetamines. STARTING DOSE: 5mg-10mg TARGET DOSING RANGE: 10mg-60mg per day BEST TIME TO DOSE: Morning (but depends on formulation) HOW TO DOSE:

>IR: Initial 5mg twice daily. Increase dose by 5mg-10mg per day each week based on response and tolerability. Typically dose every 4-6 hours. Maximum daily dose generally 40mg-60mg. Some patients may require higher dosages.



>XR: Initial 10mg every morning. Increase dose by 5mg-10mg at weekly intervals based on response and tolerability. Maximum daily dose generally 30mg-60mg. Some patients may require higher dosages.

SIDE EFFECTS: Insomnia, Headache, Anxiety/Nervousness, Abdominal Pain, Anorexia, Nausea, Vomiting, Dry Mouth, Weight loss, Seizures (rarely with PO), Psychosis (rarely with PO), Elevated Blood Pressure, Tachycardia, Sudden death has been reported in patients with preexisting cardiac structural abnormalities PREGNANCY: Avoid if possible (discuss with a medical professional) BREASTFEEDING: Avoid if possible (discuss with a medical professional) FDA INDICATIONS: 1) ATTENTION DEFICIT HYPERACTIVITY DISORDER IN CHILDREN AND ADULTS 2) NARCOLEPSY 3) EXOGENOUS OBESITY Off label: chronic fatigue, fibromyalgia, cognitive/memory problems NOTABLE INTERACTIONS: • GI/Urinary Acidifying agents decrease plasma levels of

amphetamine • GI/Urinary Alkalinizing agents increase plasma levels of

amphetamine



• Desipramine should be used with extreme caution if used with amphetamine

• Dopamine antagonists such as haloperidol and chlorpromazine as well as lithium may inhibit the stimulant effects of amphetamines

• Amphetamines increase the pain relieving effects of meperidine

• Avoid using with monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crises (extremely high blood pressures) and malignant hyperthermia (extremely high body temperatures)

ADDITIONAL INFORMATION: • Adderall is a mixture of the two isomeric forms of

amphetamine (D and L Amphetamine) in a ratio of 3 to 1 (D to L)

(D) AMPHETAMINE (DEXEDRINE)

*IR (INSTANT RELEASE) | ER (EXTENDED RELEASE) HALF-LIFE: 10-12 hours TIME TO EFFECT: IR ~1 hour | ER ~1-2 hours PEAK IN PLASMA: IR 3 hours | ER 7 hours DURATION OF CLINICAL ACTION: IR 3-9 hours | ER 6-10 hours



WITH/WITHOUT FOOD (PO): Taking with food may delay peak actions. pH of food alters absorption and elimination of amphetamines. GI and urinary Acidifying agents decrease plasma levels of amphetamines. GI and urinary alkalinizing agents increase plasma levels of amphetamines. STARTING DOSE: 5mg-10mg TARGET DOSING RANGE: 5mg-40mg per day BEST TIME TO DOSE: Morning (but depends on formulation) HOW TO DOSE:

>IR: Initial 5mg twice daily. Increase dose by 5mg-10mg per day each week based on response and tolerability. Typically dose every 4-6 hours. Maximum daily dose generally 40mg-60mg. Some patients may require higher dosages. >ER: Initial 5mg-10mg every morning. Increase dose by 5mg-10mg at weekly intervals based on response and tolerability. Maximum daily dose generally 20mg-40mg. Some patients may require higher dosages.

SIDE EFFECTS: Insomnia, Headache, Anxiety/Nervousness, Abdominal Pain, Anorexia, Nausea, Vomiting, Dry Mouth, Weight loss, Seizures (rarely with PO), Psychosis (rarely with PO), Elevated Blood Pressure, Tachycardia, Sudden death has been reported in patients with preexisting cardiac structural abnormalities. Anecdotally, patients experience less peripheral sympathetic side effects (anxiety, tachycardia, tremors) with dextroamphetamine compared to Adderall (also less irritability at the end of the day)



PREGNANCY: Avoid if possible (discuss with a medical professional) BREASTFEEDING: Avoid if possible (discuss with a medical professional) FDA INDICATIONS: 1) Attention deficit hyperactivity disorder in children and adults 2) Narcolepsy Off label: chronic fatigue, fibromyalgia, cognitive/memory problems ADDITIONAL INFORMATION: • Dexedrine contains ONLY the dextro isomer of

amphetamine

LISDEXAMFETAMINE (VYVANSE)

HALF-LIFE: lisdexamfetamine (prodrug): <1 hour | dextroamphetamine (active metabolite): 10-13 hours (dextroamphetamine) TIME TO EFFECT: Variable. But generally longer than other amphetamine formulations DURATION OF CLINICAL ACTION: Variable



WITH/WITHOUT FOOD (PO): Food does not affect absorption of lisdexamfetamine, but like other amphetamines, acidification of the urine or GI tract results in more rapid clearance.

STARTING DOSE: 20mg-30mg

TARGET DOSING RANGE: 20mg-70mg per day

BEST TIME TO DOSE: Morning

HOW TO DOSE: Initial 20mg-30mg every morning. Increase dose by 10mg-20mg at weekly intervals based on response and tolerability. Maximum daily dose generally 70mg. Some patients may require higher dosages.

SIDE EFFECTS: Insomnia, Headache, Anxiety/Nervousness, Abdominal Pain, Anorexia, Nausea, Vomiting, Dry Mouth, Weight loss, Seizures (rarely with PO), Psychosis (rarely with PO), Elevated Blood Pressure, Tachycardia, Sudden death has been reported in patients with preexisting cardiac structural abnormalities. Anecdotally, patients experience less peripheral sympathetic side effects (anxiety, tachycardia, tremors) with dextroamphetamine formulations compared to amphetamine mixed salts (also less irritability at the end of the day)

NOTABLE INTERACTIONS: Same as other amphetamines

PREGNANCY: Avoid if possible (discuss with a medical professional)

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BREASTFEEDING: Avoid if possible (discuss with a medical professional)

FDA INDICATIONS: 1) Attention deficit hyperactivity disorder in children andadults 2) Binge eating disorder

Off label: chronic fatigue, fibromyalgia, cognitive/memory problems

ADDITIONAL INFORMATION: • Lisdexamfetamine is an inactive prodrug, which means it

needs to be metabolized in order for it to be active • Lisdexamfetamine is metabolized primarily by

gastrointestinal (gut) enzymes to the active metabolitedextroamphetamine.

• Snorting or injecting lisdexamfetamine will not result in “highs” and therefore there is less abuse potential overall

• Anecdotally, patients experience less peripheral sympathetic side effects and anxiety with lisdexamfetamine(likely related to slower onset/offset of action but may also be due to stereospecificity of dextroamphetamine (active metabolite).

• Lisdexamfetamine 70mg is approximately equivalent to30mg of D,L-Amphetamine (Adderall)

• Some evidence suggests lisdexamfetamine may be beneficial for residual depressive symptoms (but controversial as RCTs failed to show separation from placebo in treatment resistant depression)



TYPICAL ANTIPSYCHOTICS

Generic Name Brand Name

Chlorpromazine Thorazine

Fluphenazine Prolixin

Haloperidol Haldol

Loxapine Loxatane

Perphenazine Trilafon

Pimozide Orap

Thiothixene Navane

Trifluoperazine Stellazine

The Typical (first-generation) antipsychotics are derived from a number of chemical classes but differ in their affinity (or potency) for binding to dopamine (D2) receptors in the brain. High Potency antipsychotics include Haloperidol and Fluphenazine whereas Low Potency antipsychotics include Chlorpromazine.

Unfortunately, the lower potency antipsychotics such as chlorpromazine (Thorazine) target more than just dopamine receptors which means they also cause a lot ofother side effects.

SAMPLE



SIDE EFFECTS OF TYPICAL ANTIPSYCHOTICS

Sedation Weight Gain Increased Appetite Blood Pressure Changes and Lightheadedness Dry Mouth Urinary Retention/Difficulty Urinating Constipation Blurry Vision Cognitive Impairment Slowed Movements (Parkinsonism) Emotional “Blunting” or “Flattening” Seizures (rare) Cardiac Arrhythmias (rare) Tardive Dyskinesia

RECEPTORS AND SIDE EFFECTS

Blockade of Histamine (H1) receptors causes sedation and weight gain

Blockade of Adrenergic (α1) receptors causes sedation and blood pressure changes

Blockade of Muscarinic cholinergic (M1) receptors causesdry mouth, urinary retention, constipation, blurry vision, and cognitive impairment/memory impairment.

SAMPLE



High-potency antipsychotics such as fluphenazine and

haloperidol show far less sedation, hypotension, and anticholinergic side effects, but because they are strong dopamine blockers, they are more likely to cause side effects from blocking dopamine (slowed movements, cognitive problems, emotional flattening, dystonic reactions, prolactin elevations, and tardive dyskinesia).

TARDIVE DYSKINESIA (TD)

Tardive Dyskinesia (TD) is a hyperkinetic movement

disorder associated with long term use of antipsychotics and/or the rapid withdrawal of antipsychotic medications.

Symptoms include involuntary movements such as lip

smacking, eye blinking, grimacing, tongue movements, or writhing movements of the extremities or trunk.

All first-generation antipsychotics induce tardive dyskinesia

(TD) at an incidence rate of about 3% to 5% per year of exposure up to 60% lifetime prevalence.

TD is mild and non-progressive in majority of cases. TD results from chronic blockade of dopamine receptors in

the brain and the body’s response to such blockade over time.



Once TD is well-established, withdrawal of the offending agent does not typically result in a return of the nigrostriatal pathway to baseline signal transduction, i.e. movements tend to persist.

TD is treated by reducing the dose of the antipsychotic,

switching to an atypical antipsychotic, or using new medications such as Valbenazine (Ingrezza).

Clozapine has been shown to reduce TD symptoms in some

patients. In general, extrapyramidal symptoms are treated by

reducing the dose of antipsychotic, switching to an atypical antipsychotic with lower dopamine blocking properties, and/or administering an anticholinergic agent such as benztropine (Cogentin) or diphenhydramine (Benadryl).

NEUROLEPTIC MALIGNANT SYNDROME (NMS)

First generation antipsychotic medications, especially high-

potency medications, may rarely induce a condition called neuroleptic malignant syndrome (NMS). Note that immediate withdrawal of dopamine agonists (such as L-Dopa or Bromocriptine) can also lead to NMS.

NMS is characterized by delirium/confusion, muscle rigidity,

rhabdomyolysis (muscle break down), fever, seizures, and renal failure.



4. Intense or prolonged psychological distress at exposure to internal or external cues.

5. Marked physiological reactions to internal or external cues.

C. Avoidance symptoms, persistent (one or both): 1. Avoidance of or efforts to avoid distressing memories,

thoughts, or feelings about or closely associated with the traumatic event(s).

2. Avoidance of or efforts to avoid external reminders (people, places, conversations, activities, objects, situations) that arouse distressing memories, thoughts, or feelings about or closely with the traumatic event(s).

D. Negative alterations in cognitions and mood as evidenced by two (or more) of the following:

1. Inability to remember an important aspect of the traumatic event(s) (typically due to dissociative amnesia and not to other factors such as head injury, alcohol, or drugs).

2. Persistent and exaggerated negative beliefs or expectations about oneself, others, or the world.

3. Persistent, distorted cognitions about the cause or consequences of the traumatic event(s) that lead the individual to blame himself/herself or others.

4. Persistent negative emotional state (e.g., fear, horror, anger, guilt, or shame).

5. Markedly diminished interest or participation in significant activities.

6. Feelings of detachment or estrangement from others. 7. Persistent inability to experience positive emotions (e.g.,

inability to experience happiness, satisfaction, or loving feelings).



E. Marked alterations in arousal and reactivity as evidenced by two (or more) of the following:

1. Irritable behavior and angry outbursts (with little or no provocation) typically expressed as verbal or physical aggression toward people or objects.

2. Reckless or self-destructive behavior. 3. Hypervigilance 4. Exaggerated startle response. 5. Problems with concentration. 6. Sleep disturbance (e.g., difficulty falling or staying asleep

or restless sleep).

F. Duration of the disturbance (Criteria B, C, D and E) is more than one month.

G. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

H. The disturbance is not attributable to the physiological effects of a substance (e.g., medication, alcohol) or another medical condition.

Specify whether:

With dissociative symptoms: Depersonalization: Persistent or recurrent experiences of feeling detached from, and as if one were an outside observer of, one’s mental processes or body (e.g., feeling as though one were in a dream; feeling a sense of unreality of self or body or of time moving slowly). Derealization: Persistent or recurrent experiences of unreality of surroundings (e.g., the world around the



individual is experienced as unreal, dreamlike, distant, or distorted).

With Delayed Expression:

If the full diagnostic criteria are not met until at least 6 months after the event (although the onset and expression of some symptoms may be immediate).



ICD-10 CODES

NEURODEVELOPMENTAL DISORDERS

Intellectual Disability

• mild F70

• moderate F71

• severe F72

• profound F73

Global dev’al delay F88

Unsp’d intel’al disabil. F79

Communication Disorders

Language disorders F80.9

Speech Sound do F80.0

Childh onset flu’cy do F80.81

Social (Pragmatic)

communication do F80.89

Unspec’d commun. Do F80.9

Autism spectrum do F84.0



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