23 Psychiatry
23.1 Consulting Psych
- Place “Psychiatry Consult” order in PowerChart. Will allow you to select an indication (including Agitation plan, Psychiatric Disposition, etc). What you write in Order Comments = what Psych uses to prioritize urgency and assign consult. Must obtain patient/guardian consent prior to placing consult.
- If patient seen in ER by Psych SW and officially boarding for inpatient LOC, as of Sept 2020 this is a new option to select on consult order
- Reasons to page Psych on-call on nights/wknd: Severe agitation, active SI w/ plan/intent, psychosis, behavior interfering w/ essential medical care
23.2 A/P Template for Patients Awaiting Inpatient Psych Placement
Use the Behavioral Healthy Safety Plan order set!
Assessment: _ is a _ y/o M/F w/ PMH __ who presents w/ concerning __ SI that makes him/her unsafe for discharge home. S/He has been medically cleared and is awaiting placement at an inpatient psychiatric facility. We will continue to provide a safe environment and follow along w/ Psychiatry.
Plan:
– Medical clearance - Utox, urine HCG - EKG (document baseline QTc)
– Behavioral plan - Supervision: 1:1 sitter vs. security, safety tray, safety check prior to any room changes - Activity level: Start w/ confined to room (Psych will decide when out-of-room privileges are ok, e.g. supervised walks around unit or visit to playroom at RN’s discretion - Electronics: Start w/ no phone or internet (Psych will decide if/when permitted and w/ what level of supervision/restrictions)
– Agitation plan, per Psychiatry on [date] - Mild agitation: Utilize behavioral strategies - Moderate agitation: Ativan OR Haldol , ALWAYS WITH Benadryl . Call BRT to help prevent further escalation to severe agitation. - Severe agitation: Olanzapine PO/IM (Zydis ODT for PO) OR Haldol PO/IM , ALWAYS WITH Benadryl PO/IM PRN. Call 5-5555 to activate Behavioral Rapid Response (summons Psych, BRT, Security). Call on-call Psych if requires IM or if not responding within 20-30min or if need further guidance. - If administering antipsychotics, daily EKG to monitor QTc (target < 450) - PO’s should be ordered as PRNs, IM must be one-time in the moment and can only be ordered by PGY2 or higher
– Dispo: pending placement to inpatient psych when available bed identified
Note: dosing for agitation meds is written as __ mg q_ NTE __ from all sources in 24hrs. Dosing recommendations per table below:
23.3 Agitation
23.3.1 Identifying Agitation
Mild: Pacing, worrying, agitated but cooperative Moderate: Swearing, threatening, yelling, screaming, clenching fists, pacing, superficial self-injury, request for meds Severe: Imminent risk of harm to self or others, aggression to others/self, destruction of property
23.3.2 Non-Pharm Management
BRT is your best friend!
23.3.2.1 Prevention
Identifying triggers:
Stimuli that trigger upsetting feelings or problematic behaviors (precipitant to behavior)
Environmental or emotional
Patients at risk: ASD, developmental delay, trauma
Think about the 4 functions of any behavior: Attention, escape, sensory, tangibles/access
23.3.2.2 Ways to respond
Recognize and respond to initial signs of agitation or inappropriate behavior w/ redirection. Avoid using the word “no.” Avoid non-specific comments such as “behave” or “calm down”
Ignore behavior that is disruptive, but not harmful. Make a blank non-smiling face, avoid eye contact and turn away. As soon as the child stops the unwanted behavior, smile and make eye contact. Give the child a space - somewhere calm and safe - where they can go when they feel overwhelmed. Do not simply react; try to understand the reasons behind the behavior.
23.3.2.3 Managing the situation
Managing the situation Start by asking “what do you want?” Try the SAVE mnemonic: Support ”Let’s work together…”, Acknowledge “I see this has been hard for you.” Validate ”I’d probably be reacting the same way if I was in your shoes.”, Emotion naming ”You seem upset.” or similar communication efforts when talking with the patient.
Strategies will differ based on degree of agitation:
Mild
- Listen, validate, problem-solve
- Stay w/ the patient, have them sit w/ you
- Maintain calm demeanor
- Eliminate distractions
- Empathetic listening
- Utilize supportive eye and verbal communication, gestures, posture, and facial expressions
- Utilize preferred activities (eg music)
Moderate
- Redirect, problem-solve
- Allow individual to vent
- Validate feelings
Severe
- Direct, clear communication
- Call 5-5555 to activate Behavioral Rapid Response (summons Psych, BRT, Security)
- Maintain safe distance (4ft); intervene if danger is imminent
- Interrupt individual’s focus
- Body language techniques
- Positive verbal command
- Throwing/dropping an object
- Moving as an escape technique
- Medications (PO vs. IM), potential need for restraint.
23.3.3 Restraints
Ordering restraints for violent or self-destructive/injurious behavior:
CANNOT be written PRN! Appropriate restraint order must be placed immediately upon initiation of restraint.
Ordering clinician must perform face-to-face within 1hr
Order cannot be written by an intern, must be junior/senior resident
23.3.4 Pharmacologic Management
See A/P Template section above, as well as Rapid Reference chapter
Psychiatry will determine an appropriately tailored pharmacologic agitation plan, but these guidelines are a good starting place if you don’t yet have a formal plan in place:
23.3.4.1 Medication Recommendations - Moderate Agitation
Parenteral medication orders for agitation may not be ordered PRN. Place 1 time orders at the time the medication is needed.
| Parameter | Child (weighing 25-50 kg) | Adolescent (weighing > 50 kg) |
|---|---|---|
| Preferred Agent(s) | Diphenhydramine or Lorazepam | Diphenhydramine or Lorazepam |
| Administration Route For escalating patients who refuse PO and for whom there is significant concern for imminent and serious risk of harm to self or others, please progress to severe agitation IM plan below. IM medications usually require physical holds or restraints and should only be involuntarily administered if there is significant risk of harm |
PO | PO |
| Initial Dosing | Diphenhydramine 25 mg or Lorazepam 0.5 - 1 mg |
Diphenhydramine 50 mg or Lorazepam 1- 2 mg |
| Repeat dosing (60 minutes after initial dose if ineffective) |
Diphenhydramine 25 mg or Lorazepam 0.5 - 1 mg |
Diphenhydramine 25 mg or Lorazepam 1 – 2 mg |
| Subsequent Frequency | Q4 – 6 hours Not to exceed 100 mg of diphenhydramine or 2 mg of lorazepam in 24 hours |
Q4 – 6 hours Not to exceed 150 mg of diphenhydramine or 4 mg of lorazepam in 24 hours |
PO’s should be ordered as PRNs, IM must be one-time in the moment and can only be ordered by PGY2 or higher Prescribers to use discretion and order lower or higher doses as appropriate.
23.3.4.2 Medication Recommendations - Severe Agitation
Parenteral medication orders for agitation may not be ordered PRN. Place 1 time orders at the time the medication is needed.
| Parameter | Child (weighing 25-50 kg) | Adolescent (weighing > 50 kg) |
|---|---|---|
| Preferred Agent(s) | Olanzapine* (ODT for PO) or Haloperidol and Diphenhydramine** or Lorazepam |
Olanzapine* (ODT for PO) or Haloperidol and Diphenhydramine** and/or Lorazepam |
| Administration Route | PO or IM | PO or IM |
| Initial Dosing | Olanzapine 2.5 mg or Haloperidol 2 mg and Diphenhydramine 25 mg or Lorazepam 0.5-1 mg |
Olanzapine 5 mg (can use 7.5mg for patients weighing > 70kg) or Haloperidol 5 mg and Diphenhydramine 50 mg and/or Lorazepam 1-2 mg (can use Haloperidol, Diphenhydramine and Lorazepam combined for patients weighing > 70kg) |
| Repeat dosing (45 minutes after initial dose if ineffective***) | Olanzapine 2.5 mg or Haloperidol 1 mg and Diphenhydramine 25 mg or Lorazepam 0.5-1 mg |
Olanzapine 5 mg or Haloperidol 2.5 mg and Diphenhydramine 25 mg and/or Lorazepam 1-2 mg |
| Subsequent Frequency | Q4hr Do not exceed: Olanzapine 10 mg in 24 hours Haloperidol 5 mg in 24 hours Diphenhydramine 100 mg in 24 hours Lorazepam 3 mg in 24 hours |
Q4hr Do not exceed: Olanzapine 15 mg in 24 hours Haloperidol 10 mg in 24 hours Diphenhydramine 150 mg in 24 hours Lorazepam 6 mg in 24 hours |
Do NOT use IM olanzapine within 4 hours of IM/IV lorazepam due to risk of cardiopulmonary depression.
ODT = orally disintegrating tablet.
Use of diphenhydramine with haloperidol is preferred to haloperidol alone to avoid risk of acute dystonic reactions. The use of haloperidol in combination with Fluoxetine (Prozac) or Citalopram (Celexa) can significantly increase the risk of QT prolongation and should only be used if benefits outweigh the risks. Consult formulary for complete information.
If pharmaceutical interventions are not effective, patients at risk for self-harm or harming others may require physical restraints, turning off the lights, and an urgent psychiatry evaluation.
The use of haloperidol in combination with Fluoxetine (Prozac) or Citalopram (Celexa) can significantly increase the risk of QT prolongation and should only be used if benefits outweigh the risks.
23.4 Medications That Cause Psychiatric Side Effects
23.4.1 Selected Meds
Steroids: Aggressiveness/agitation, mania, depression, anxiety, psychosis
Procainamide, quinidine: Confusion, delirium
Albuterol: Anxiety, confusion
Isoniazid: Psychosis
Tetracycline: Depression
Nifedipine, verapamil: Depression
Cimetidine: Depression, confusion, psychosis
23.4.2 Psychosis
Sympathomimetics, analgesics, antibiotics (e.g. isoniazid, antimalarials), anticholinergics, anticonvulsants, antihistamines, corticosteroids, antiparkinsonian agents.
23.4.3 Agitation/Confusion/Delirium
Benzos, antipsychotics, anticholinergics, antihistamines, antidepressants, antiarrhythmics, antineoplastics, corticosteroids, NSAIDs, antiasthmatics, antibiotics, antihypertensives, antiparkinsonian agents, thyroid hormones
23.4.4 Depression
Antihypertensives, antiparkinsonian agents, corticosteroids, calcium channel blockers, NSAIDs, antibiotics, peptic ulcer drugs.
23.4.5 Anxiety
Sympathomimetics, antiasthmatics, antiparkinsonian agents, hypoglycemic agents, NSAIDs, thyroid hormones.
23.4.6 Sedation/Poor concentration
Antianxiety agents/hypnotics, anticholinergics, antibiotics, antihistamines.
23.5 Capacity Assessment
Capacity vs competency: Capacity is a one-time assessment by a clinician. Competency is a legal decision based on accumulated evidence that requires court hearing/proceeding.
| Patient (18yo+)/family must… | Assessment |
|---|---|
| Communicate a clear and stable choice | Ask patient to indicate a choice. Frequent reversals may indicate lack of capacity. |
| Understand relevant information | Ask patient to explain their understanding of the information given by physician (diagnosis, prognosis, proposed intervention, risks/benefits of intervention and alternatives, including no intervention) |
| Appreciate the situation and its consequences | |
| Manage the information in a rational manner | Does patient weigh risks/benefits logically? |
| Is there true imminent risk? | EX: patient indicating they are suicidal but meet all 4 criteria above. |
23.6 Depression & Anxiety
23.6.1 Diagnosis
Major Depressive Episode: 2 wks of: Depressed mood (or irritability, which is more common in children) OR anhedonia, PLUS 4+ of remaining SIGECAPs (Sleep change, Interest loss, Guilt/worthlessness, Energy loss/fatigue, Cognition/concentration, Appetite change, Psychomotor change, SI) - Ddx: Hypoactive type (wax/wane, acute-onset, possibly 2/2 underlying medical illness or iatrogenic), adjustment disorder (needs psychotherapy only), delirium
23.6.2 Management
According to TADS and CAMS (2 large RCTs w/ govt oversight), combination therapy of SSRI + CBT is superior to monotherapy w/ either! CBT or SSRI is superior to placebo. No SSRI-associated suicidal events in either study, but when initiating SSRI it is important to monitor carefully (wks 1-4: weekly; wks 5-12: every other week) for any signs of ↑ suicidality - NEVER prescribe paroxetine (Paxil) to adolescents (black box warning for suicide)
SSRIs are 1st line: Help ⅔ of pts in first trial over 4-8 wks. ⅔ of nonresponders respond to 2nd trial. - Sertraline (Zoloft) and Fluoxetine (Prozac) are most commonly used, least SE (used in TADS, CAMS). - Mild serotonergic side-effects (hyperhidrosis, nausea, headache, tremulousness, diarrhea) can happen w/ SSRI/SNRI initiation and/or uptitration, usually goes away in 2-3 days
23.7 Suicide
- If you don’t directly ask about suicide, you won’t hear about it. NEVER assume! You don’t have to be depressed to be suicidal.
- ~4% of patients coming in to ED (for all complaints) are suicidal.
- Adolescents more likely to kill selves by firearm; children by strangulation
ASQ: Adolescent Suicide Screening Tool In the past few weeks, have you wished you were dead? In the past few weeks, have you felt that you or your family would be better off if you were dead? - Yes to 1 or 2 (passive SI): Counsel, supportive listening, referrals In the past week, have you been having thoughts about killing yourself? Have you ever tried to kill yourself? Are you having thoughts of killing yourself right now? - Yes to 3 or 5 (active SI): Immediate consult from ER/floor/outpt mental health clinician
23.8 Antidepressants
23.8.1 Selective Serotonin Reuptake Inhibitors (SSRIs)
23.8.1.1 Mechanism of Action
5-HT-specific reuptake inhibitor
23.8.1.2 Use
Depression, Gen. anxiety disorder, Panic disorder, OCD, bulimia, social anxiety disorder, PTSD, premature ejaculation, premenstrual dysphoric disorder
- It normally takes 4–8 weeks for antidepressants to have full effect.
Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Citalopram (Celexa), Escitalopram
(Fl ashbacks par alyze se nior cit izens)
Paroxetine → short half-life → discontinuation syndrome (flu-like sxs, dizzy, diaphoretic, “electric shock,” + depression). Do not use in adolescents due to black box warning for suicide.
Fluoxetine → long half-life → no need to taper/good for poor compliance, P450 inhibitor, can ↑antipsychotics → ↑SEs
Citalopram/Escitalopram → Dose dependent QTc prolongation (usually minimal)
23.8.1.3 Side Effects
GI distress, SIADH, sexual dysfunction (anorgasmia, ↓ libido), insomnia, anorexia, ↑ suicidality in adolescents , QTc prolongation, mildly ↓ Na (i.e. 128)
Serotonin syndrome: 2 meds that ↑ serotonin (MAOis, SNRIs, TCAs, Opoids, Tramadol, Linezolid) → ↑↑ serotonin in brain. (ex: triptan/SSRIs)
3 A’s: neuromuscular Activity (clonus, hyperreflexia, hypertonia, tremor, seizure), Autonomic stim (hyperthermia, diaphoresis, diarrhea), and Agitation. Tx: cyproheptadine (5-HT2 receptor antagonist) or benzodiazepines
23.8.2 Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
23.8.2.1 Mechanism of Action
Inhibit 5-HT and NE reuptake
23.8.2.2 Use
Depression, general anxiety disorder, diabetic neuropathy. Venlafaxine → also indicated for social anxiety disorder, panic disorder, PTSD, OCD, menopausal depression (b/c of NE effects) Duloxetine → also used for neuropathy (vs. Amitriptyline is better in suicidal patient who might overdose)
23.8.2.3 Examples
Venlafaxine (Effexor), Duloxetine (Cymbalta), desvenlafaxine, levomilnacipran, milnacipran.
23.8.2.4 Side Effects
↑ BP most common; also stimulant effects, sedation, nausea
23.8.3 Tricyclic Antidepressants (TCAs)
23.8.3.1 Mechanism of Action
Block reuptake of NE and 5-HT. (-triptyline, -pramine –doxepin)
23.8.3.2 Use
Major depression, OCD (clomipramine), peripheral neuropathy, chronic pain, migraine prophylaxis.
23.8.3.3 Examples
3° amines: -Amitriptyline (pain/migraines), Imipramine (enuresis), clomipramine (OCD), doxepin 2° amines: -Nortriptyline, amoxapine, desipramine (ADHD)
23.8.3.4 Side Effects
Tri-C’s: CNS toxicity (Convulsions/Coma), Cardiotoxicity (arrhythmia -Na+ channel inhib, ↑QT int), antiCholinergic (urinary retention); Sedation, α1-blocking effects (postural hypotension), anticholinergic SEs (tachycardia, urinary retention, dry mouth) 3° TCAs (amitriptyline) have more anticholinergic effects than 2° TCAs (nortriptyline). QRS duration >100 msec → assoc. w. ↑risk of arrhythmias and/or seizures =indication for Tx: NaHCO3-stabilizes myocardium, alkalinize urine Confusion/hallucinations in elderly due to anticholinergic side effects (use nortriptyline)
23.8.4 Monoamine Oxidase Inhibitors (MAOIs)
Note: Rarely used anymore
23.8.4.1 Mechanism of Action
Nonselective MAO inhibition → ↑ levels of amine neurotransmitters (NE, 5-HT,dopamine)
23.8.4.2 Use
Atypical depression (hypersomnia, ↑ appetite, heavy extremities, ↑ sensitivity to interpersonal rejection) Anxiety - Selegiline → only antidepressant that comes in dermal patch form (good for patient that cannot tolerate PO)
23.8.4.3 Examples
Phenelzine, Isocarboxazid, Tranylcypromine, (MAO Takes Pride In Shanghai), Selegiline (selective MAO-B inhibitor – Parkinson’s, Transdermal).
23.8.4.4 Side Effects
Hypertensive crisis (tyramine (cheese, wine)) → ↑↑ BP, HA, sweating, N/V, photophobia, autonomic instability, stroke/death Tx: Nitroprusside, Phentolamine Serotonin Syndrome: MAOIs are contraindicated in combo w/ SSRIs, TCAs, Tramadol, Linezolid, St. John’s wort, meperidine, dextromethorphan - Wait 2 weeks after stopping MAO inhibitors before starting serotonergic drugs or stopping dietary restrictions. Linezolid is a weak MAOI, and warrants avoidance of norepi and serotonergic drugs (big problem in CF patients w/ depression), otherwise risk hypertensive urgency and/or serotonin syndrome, respectively
23.8.5 Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)
23.8.5.1 Mechanism of Action
↑ norepinephrine and Dopamine via unknown mechanism
23.8.5.2 Use
MDD w/ sexual side effects from SSRI’s, MDD w/ wt gain/hypersomnia (bupropion is PRO penis, not Bulemic). Smoking cessation.
23.8.5.3 Examples
Bupropion (Wellbutrin)
23.8.5.4 Side Effects
Seizures (in anorexic/bulimic or hx seizures), stimulant effects (tachycardia, insomnia), headache No sexual side effects
23.8.6 Alpha2-Adrenergic Receptor Antagonists
23.8.6.1 Mechanism of Action
α2-antagonist (↑release of NE and 5-HT), potent 5-HT2 /5-HT3 receptor antagonist and H1 antagonist (sleepy/appetite effects)
23.8.6.2 Use
Major depression (especially in patient w/ weight loss and/or insomnia) → EX: cancer patient w/ N/V, ↓appetite, + MDD
23.8.6.3 Examples
Mirtazapine (Remeron)
23.8.6.4 Side Effects
Sedation (desirable in depressed patients w/ insomnia), ↑appetite, wt gain (may be desirable in elderly/anorexic), dry mouth.
23.8.6.5 Notes
Adrenergics like guanfacine and clonidine are very useful in hyperactive ADHD and sometimes PTSD/irritability in general. Mirtazapine/Remeron is a multi-receptor drug and most of its psychotropic effect is from 5-HT activity, actually.
23.8.7 Serotonin Receptor Antagonists and Agonists
23.8.7.1 Mechanism of Action
Primarily blocks 5-HT2, α1-adrenergic, and H1 receptors; also weakly inhibits 5-HT reuptake.
23.8.7.2 Use
Insomnia (high doses are needed for antidepressant effects)
23.8.7.3 Examples
Trazodone (Desyrel) and Nefazodone (Serzone)
23.8.7.4 Side Effects
Sedation, nausea, priapism, postural hypotension. Called traZZZoBONE → b/c sedative and male-specific side effects.
23.8.8 Nicotinic ACh Receptor Partial Agonist
23.8.8.1 Use
Smoking cessation
23.8.8.2 Examples
Varenicline (Chantix)
23.8.8.3 Side Effects
Sleep disturbance, mood changes, suicidality, cardiovascular events
23.9 Antipsychotics
23.9.1 Typical Antipsychotics (1st Generation)
23.9.1.1 Mechanism of Action
Block D2 receptors (↑[cAMP]) → Low/High Potency can cause QT prolongation(450 = number you are looking for)
23.9.1.2 Use
Schizophrenia (helps positive sx, little effect on neg sx), psychosis, bipolar disorder, delirium, Tourette syndrome, Huntington disease, OCD
23.9.1.3 Low Potency
Chlorpromazine,(Corneal deposition), Thioridazine(reTinal deposition) → Cheating Thieves are LOW - Blocks HAM – Histamine (sedation), α1 (orthostatic hypoTN), Muscarinic (dry mouth, constipation)
23.9.1.4 High Potency
Trifluoperazine, Fluphenazine, Haloperidol → Try to Fly High
- Libido, osteoporosis, amenorrhea, gynecomastia Tuberoinfundibular: block dopa → ↑ prolactin→ ↓GnRH → ↓ FSH/LH
- Extrapyramidal symptoms - Nigrostriatal: ACTH/dopamine in balance → block dopamine → ↑ACTH
| ADAPT | Time | Extrapyramidal Symptoms | Management |
|---|---|---|---|
| Acute Dystonia | Hrs-days | Muscle spasm, torticollis, stiffness, oculogyric crisis | IM: (1) Benztropine (2) Diphenhydramine (antihistamine and anticholinergic effects) (3) Lorazepam |
| Akathisia | Days -mos | Restlessness, ↑risk for suicide | Propranolol |
| Parkinsonism | Days- mos | Bradykinesia, tremor, rigidity, mask-like facies, | 1. Benztropine (NOT L-dopa b/c ↑ dopamine → ↑ psychosis) 2. Trihexyphenidyl, maybe amantadine |
| Tardive dyskinesia | Mos-yrs | Repetitive orofacial movements - dopamine hypersensitivity | 1. STOP antipsychotic (may worsen when first stop) 2. START atypical -> Quetiapine or Clozapine |
Neuroleptic malignant syndrome: Fever (>103), Rigidity, ↑ CPK → rhabdo, AKI - Due to dopamine dysregulation. Caused by: typical/atypical antipsychotics, antiemetics, antiparkinson med withdrawal, infection, surgery - FEVER: Fever, Encephalopathy (AMS), Vitals unstable, ↑ Enzymes, Rigidity (lead pipe), leukocytosis - Compare to Serotonin Syndrome → NMS (↑↑Rigidity), SS (↑DTRs/clonus, GI sxs) - Tx; (1) STOP drug (most important intervention) (2) Hydrate, cooling blankets If no response to stopping drug →(3) Dantrolene (inhibition of Ca2+ release)/ Bromocriptine/Amantadine (4) ECT
23.9.1.5 Notes
IV and IM carry more risk of QTc and torsades than PO Our hospital has policy that only can get IV haloperidol while on telemetry (ICUs and 8E)
23.9.2 Atypical Antipsychotics (2nd Generation)
23.9.2.1 Mechanism of Action
Blocking D2 receptor AND serotonin 2A receptor blockade
23.9.2.2 Use
Schizophrenia (better neg sx coverage than typicals), bipolar disorder, OCD, anxiety disorder, depression, mania, Tourette syndrome
23.9.2.3 Side Effects
ALL SE’s: Metabolic side effects → sleepy and fat, → W/u: EKG, Lipids, BMI - Olanzapine → Obesity (metabolic syndrome) - Risperidone → ↑prolactin (↓dopamine activity in tuberoinfundibular pathway→ gynecomastia, galactorrhea, amenorrhea) - Quetiapine → best for movement disorders (ex: Parkinson’s) - Ziprasidone → starts w/ Z worst for the qTC, ↓metabolic effects - Aripiprazole → light and “ari” → doesn’t put you to sleep/lead to weight gain; partial agonist at D2 - Clozapine → D4 blockade is primary effect, must watch closely → monitor WBC and ANC – 3 good: best efficacy (if nothing else working), ↓ risk of suicide in schizophrenia (lithium only other), good for Lewy Body Dementia – 6 bad (1) Agranulocytosis (CBCd before/wkly for 1st 6 mo→ ANC <1500 → Tx: STOP. (2) Myocarditis (EKG, troponins, etc) (3) ↓ Seizure threshold (most common) (4) Wt gain (worse than olanzapine) (5) Sedation (6) Sialorrhea Others in this class not already mentioned above: Asenapine, Iloperidone, Lurasidone, Paliperidone
23.10 Mood Stabilizers
23.10.1 Lithium
23.10.1.1 Mechanism of Action
Not established; possibly related to inhibition of phosphoinositol cascade → inositol = buzzword
23.10.1.2 Use
Mood stabilizer for bipolar disorder; blocks relapse and acute manic events.
Drug of choice in acute mania and as prophylaxis for both manic/depressive episodes in bipolar & schizoaffective disorders.
It is also used in cyclothymic disorder and unipolar depression
Excellent at low doses for anti-suicidality
Contraindications: chronic kidney disease, heart disease, hyponatremia or diuretic use
Therapeutic range: 0.8-1.2 mEq/L
23.10.1.3 Side Effects
Lithium SEs: Movement (tremor), Nephrogenic Diabetes Insipidus HypOthyroidism, Pregnancy problems (Ebstein anomaly) (LMNOP). Skin problems (acne, psoriasis). - Prior to starting: ECG, BUN, creatinine, Ca2+, u/s,, thyroid function tests, CBC, and a pregnancy test Almost exclusively excreted by kidneys; most is reabsorbed at PCT w/ Na+ - ↑ Li+ levels: NSAIDs, Aspirin, Thiazides, ACEi/ARBs, Metronidazole, Dehydration, Salt depr, Sweating (salt loss), ↓renal fxn - ↓ Li+ levels: K+ sparing diuretics, Theophylline, CCB/Furosemide may ↑/↓ Acute Lithium toxicity: tremor, diarrhea, vomiting, weakness, polyuria, polydipsia, ataxia, cognitive impairment Chronic Lithium toxicity: nephrogenic diabetes insipidus, thyroid dysfunction, hyperparathyroidism
23.10.2 Valproic Acid (Depakote)
23.10.2.1 Mechanism of Action
↑ Na+ channel inactivation, ↑ GABA concentration by inhibiting GABA transaminase
23.10.2.2 Use
Bipolar (acute mania, mixed features, rapid cycling), Migraine prophylaxis, Myoclonic seizures
23.10.2.3 Side Effects
Hepatotoxicity (measure LFTs)/↑ ammonia, Hemorrhagic Pancreatitis, ↓ plts, neural tube defects, tremor, wt gain/PCOS, hair loss
23.10.3 Carbamazepine (Tegretol)
23.10.3.1 Mechanism of Action
Blocks Na+ channels
23.10.3.2 Use
Bipolar (esp. mania w/ mixed features and rapid-cycling), Antiepileptic, Trigeminal neuralgia
23.10.3.3 Side Effects
cyt P-450 inducer (↓ Warfarin effects → bleed, ↓ OCP effects → pregnancy), blood dyscrasias (agranulocytosis (↓ ANC), aplastic anemia), liver toxicity, teratogenesis, SIADH, Stevens-Johnson syndrome, Diplopia, ataxia
23.10.4 Buspirone (BuSpar)
23.10.4.1 Mechanism of Action
Stimulates 5-HT1A receptors
23.10.4.2 Use
Generalized anxiety disorder
23.10.4.3 Side Effects
Does not cause sedation, addiction, or tolerance. Takes 1–2 wks to take effect. Does not interact w/ alcohol (vs barbiturates, benzodiazepines)
23.10.5 Benzodiazepines
23.10.5.1 Mechanism of Action
Facilitate GABA-A action by ↑ freq of Cl− channel opening. ↓ REM sleep. “Frenzodiazepines” ↑ frequency. Benzos, barbs, and alcohol all bind the GABA-A receptor, which is a ligand-gated Cl− channel. Most have long half-lives/active metabolites (except: Alprazolam, Triazolam, Oxazepam, Midazolam→ short acting, ↑ addictive potential)
23.10.5.2 Use
Anxiety, akathisia, spasticity, status epilepticus (Lorazepam, diazepam), eclampsia, detoxification (esp. alcohol withdrawal/DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia)
23.10.5.3 Examples
Diazepam (Valium), Clonazepam (Klonopin), Lorazepam (Ativan), temazepam, oxazepam (safer for impaired liver), midazolam (Versed), triazolam, chlordiazepoxide (long-acting, used to treat EtOH withdrawal, but not in liver failure), Alprazolam (Xanex).
23.10.5.4 Side Effects
Dependence, Additive CNS depression effects w/ alcohol (drowsiness, impaired intellect, motor coordination, amnesia) - Less risk of respiratory depression and coma than in barbiturates.
Overdose tx: Flumazenil (competitive antagonist at GABA benzodiazepine receptor) - Can precipitate seizures by causing acute benzodiazepine withdrawal → withdrawal can be life threatening
23.10.6 Barbiturates
23.10.6.1 Mechanism of Action
Facilitate GABA-A action by ↑ duration of Cl− channel opening → ↓ neuron firing (barbiturates → ↑ duration). Contraindicated in porphyria.
23.10.6.2 Use
Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
23.10.6.3 Examples
Phenobarbital, pentobarbital, thiopental, secobarbital
23.10.6.4 Side Effects
Respiratory/cardiovascular depression (can be fatal); CNS depression (exacerbated by alcohol use); dependence - Drug interactions (induces cytochrome P-450)
Overdose Tx: supportive (assist respiration and maintain BP)
23.10.7 Non-Benzodiazepine Hypnotics
23.10.7.1 Mechanism of Action
Act via the BZ1 subtype of the GABA receptor. Effects reversed by flumazenil. Sleep cycle less affected as compared w/ benzodiazepine hypnotics
23.10.7.2 Use
Insomnia. Should be used short-term (weeks-months), although ↓ risk of dependence compared to benzos as sleep aid.
23.10.7.3 Examples
Zolpidem (Ambien), Zaleplon (Sonata), esZopiclone (Lunesta). “All ZZZs put you to sleep.”
23.10.7.4 Side Effects
Sleep-walking, ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects.
23.11 Other Psychotropic Medications
23.11.1 Stimulants
23.11.1.1 Mechanism of Action
↑ catecholamines in the synaptic cleft, especially norepinephrine and dopamine
23.11.1.2 Use
ADHD, narcolepsy (modafinil), appetite control
23.11.1.3 Examples
Methylphenidate (Ritalin, Concerta), Dextroamphetamine (Adderall), methamphetamine, Modafinil (Provigil). Atomoxetine (Strattera) is not technically a stimulant, in its own class.
23.11.1.4 Side Effects
Hypertension, weight loss, insomnia, exacerbation of tics, ↓ seizure threshold
23.11.2 Acetylcholinesterase Inhibitors
23.11.2.1 Mechanism of Action
Inhibits AChE → ↑ ACh in synaptic cleft
23.11.2.2 Use
Mild-moderate dementias (neurocognitive disorders) → ex: Alzheimer’s (Donepezil/Rivastigmine)
23.11.2.3 Examples
Donepezil (Aricept), Galantamine (Razadyne), Rivastigmine (Exelon)
23.11.3 NMDA (Glutamate) Receptor Antagonist
23.11.3.1 Mechanism of Action
Antagonist at NMDA (glutamate) receptor
23.11.3.2 Use
ADHD, narcolepsy (modafinil), appetite control
23.11.3.3 Examples
Memantine (Nemenda)
23.12 Electroconvulsive Therapy (ECT)
23.12.1 Definition
Small electric current to produce generalized seizure for 20-30 seconds under general anesthesia
23.12.2 Indications
Used in: Unipolar/bipolar depression, catatonia, bipolar mania. For: Treatment resistance, psychotic features, emergent conditions (pregnancy, refusal to eat/drink, imminent risk for suicide), pharmacotherapy contraindicated due to comorbid illness/poor tolerability, hx of ECT response.
23.12.3 Safety
No absolute contraindications Increased risk: severe cardiovascular disease, recent MI, space-occupying brain lesion, recent stroke, unstable aneurysm
23.12.4 Side Effects
Most common: amnesia (anterograde or retrograde; anterograde resolves rapidly, retrograde persists) – rare w/ unilateral ECT and many experts think repeated general anesthesia may be major contributor
23.13 Psychotherapy
| Modality | Duration | Patient | Focus |
|---|---|---|---|
| Cognitive behavioral therapy (CBT) | Time limited | Anxiety, mood, personality, somatic symptom, eating disorder Maladaptive thoughts, avoidance behavior, ability to participate in homework |
Combines cognitive/behavioral tech Challenges maladaptive thoughts Targets avoidance w/ behavioral techniques (relaxation, exposure) |
| Dialectical behavioral therapy (DBT) | Varies | Borderline personality disorder; self-injury | Improves emotion regulation, mindful awareness, distress tolerance Manages self-harm |
| Interpersonal psychotherapy | Time limited | Depressed w/ relationship conflicts | Links current relationships conflicts to depressive symptoms |
| Supportive psychotherapy | Ongoing | Lower functioning; in crisis, psychotic | Therapist as guide Reinforces coping skills / builds adaptive defenses |
| Motivational interviewing | Varies | Substance use disorder | Addresses ambivalence and enhances motivation to change Nonjudgmental; acknowledge resistance |
| Biofeedback | Varies | Prominent physical symptoms; pain disorders | Improves awareness and control over physiological reactions Lowers stress levels, integrates mind/body |