Side Effects of Atypical Antipsychotics

antipsychotics

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Atypical (a.k.a., “second-generation”) antipsychotics are commonly used in the treatment of psychotic disorders, and mood disorders as well. Compared to typical (first-generation) antipsychotics, the atypical antipsychotics have lower affinity for dopamine D2 receptors, and they also act at serotonin (5-HT) receptors (they are antagonists for these receptors). Other neurotransmitter receptors are affected as well, and each atypical antipsychotic preferentially antagonizes different receptors.

When atypical antipsychotics were first introduced, it was hoped that they would be more effective than typical antipsychotics and have fewer extrapyramidal side effects (see below). While these expectations may have been somewhat overblown and atypicals are not markedly superior in decreasing psychosis symptoms, most atypicals certainly have a lower risk of developing extrapyramidal side effects. However, they do come with their own array of side effects.

Extrapyramidal side effects (EPSE): These are movement-related side effects caused by dopamine antagonism. These include acute dystonia (torticollis, an uncomfortable muscular spasm of the neck; as well as spasms of the eyes, tongue, jaw), akathisia (motor restlessness and a need to remain in motion), tardive dyskinesia (repetitive, involuntary movements usually involving facial muscles), parkinsonian symptoms (resting tremor, rigidity, slowed movements), and neuroleptic malignant syndrome (potentially fatal!).
Elevated prolactin (PRL): This can lead to gynecomastia (breast growth) and galactorrhea (milk-production), which can be very distressing for male patients! Can also cause infertility and sexual dysfunction. It also happens with typical antipsychotics.
Weight gain: This can be very a troublesome symptom, and may lead to diabetes in some patients.
Sedation: This may prevent patients from engaging in their usual activities and work.
Orthostatic hypotension: Drop in blood pressure after standing from sitting position.

Some antipsychotics have especially severe side effects. Clozapine, for example, is extremely effective in treating psychosis but can lead to fatal agranulocytosis (drop in white blood cells), as well as tremendous weight gain and sedation. Ziprasidone use can lead to QTc prolongation and increase the risk for serious cardiac arrhythmia.

The above chart shows the relative side effect profiles of eight atypical antipsychotics (aripiprazole, clozapine, lurasidone, olanzepine, paliperidone, quetiapine, risperidone, ziprasidon) versus two typical antipsychotics (chlorpromazine, haloperidone).

  • Haddad PM, Sharma SG. 2007. Adverse effects of atypical antipsychotics: Differential risk and clinical  implications. CNS drugs; 21:911.
  • Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lassig B, Salanti G, Davis JM. 2013. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple treatments meta-analysis. Lancet; 382:951.
  • Meltzer HY. 2013. Update on typical and atypical antipsychotic drugs. Annual Review of Medicine: 64:393.
  • Sadock BJ, Sadock VA (Eds.). 2007. Serotonin-dopamine antagonists: Atypical antipsychotics. In: Kaplan & Sadock’s Synopsis of Psychiatry. Lippincott Williams & Wilkins, Philadelphia PA.

The Standard Drink

standard_drink

A “standard drink” is a measure of pure ethanol consumed. One standard drink represents 10 grams of pure ethanol.

This means that based on the alcohol percentage of certain drinks, the “standard” size changes. The important thing to be aware of is to think of it as a Standard Drink because the size that equals 10 g of ethanol isn’t necessarily the standard size that is served. This is why it’s a good habit when asking “how many glasses of _______ do you drink” to ask about the size of the glass.

This design was actually originally made for an event, but I’m reposting it here because it’s useful and I like it and I haven’t had a chance to draw anything new recently.

Serotonin Syndrome

Serotonin syndrome is a serious and life-threatening reaction caused by excess serotonin in the CNS.

The classic triad

  1. Mental status changes (anxiety, restlessness, delirium, easy to startle)
  2. Autonomic hyperactivity (hyperthermia, hypertension, tachycardia, diaphoresis, vomiting, diarrhea)
  3. Neuromuscular abnormalities (hyperreflexia, myoclonus, tremor, muscle rigidity, and bilateral Babinski sign) – more pronounced in lower extremities
Serotonin Syndrome Neuroleptic Malignant Syndrome
Onset <24 H Days to weeks (not
Neuromuscular Hyperreactivity (tremor, clonus) Severe muscle rigidity, hyporeactivity (bradyreflexia)
Cause SSRIs, TCAs, MAOIs, other serotonergic drugs Dopamine antagonists (antipsychotics)
Lab findings None Elevated CK
Treatment STOP AGENT! Benzodiazepines +/- Propranolol STOP AGENT! + Bromocriptine +/- Dantrolene
Resolution Within 24h Days to week

 

 

Biopsychosocial Formulation for Psychiatry (with printable PDF)

The biopsychosocial model for psychiatry is a way to formulate what factors are in play in an individual’s illness. It can also be used as a way to approach what aspects you need to consider when deciding on a treatment plan.

The biological factors include things such as genetics, general medical conditions and drugs (pharmacotherapy).

The psychological factors include a person’s coping strategies, personality and therapy (cognitive behavioural therapy, psychodynamic psychotherapy, dialectic behavioural therapy, etc).

The social factors include a person’s living situation, their support (both family and friends), finances, situation at work/school, etc.

 

And because that’s a teeny weeny image, here is a lovely PDF to download and print:

DOWNLOAD PDF TO PRINT

Bipolar I, II, and Cyclothymia

First thing’s first, it is important to understand the difference between a mood episode and a mood disorder.

Mood Episodes

The best way is to think of the episodes as the building blocks of the disorders.

Major Depressive Episode: 2 week period of depressed mood OR anhedonia plus 4 other symptoms of MSIGECAPS (useful mnemonic)

  • Mood (low)
  • Sleep (decreased)
  • Interest (decreased)
  • Guilt
  • Energy (low)
  • Concentration (poor)
  • Appetite (decreased)
  • Psychomotor retardation or agitation
  • Suicidal ideation

Manic Episode: 1 week period of elevated or irritable mood with 4 or more of (mnemonic  GST PAID)

  • Grandiose thoughts
  • Sleep, decreased need for
  • Talkative
  • Pleasurable activities with Painful consequences (gambling, spending lots of money, having lots of sex)
  • Activity increased
  • Ideas (flight of)
  • Distractability

Hypomanic Episode: Same as manic except dialled down a notch. Only needs to be 4 days with 3 or more symptoms. People can still function and generally like being hypomanic, but their friends and family will notice a difference in them.

Mixed Episode: BOTH manic episode and major depressive episode at the same time (as in during the same day they’ll experience both depression and mania) in 1 week.

Mood Disorders

Bipolar I

  • 1 manic episode OR 1 mixed episode
  • Treatment: mood stabilizer (lithium or anti-convulsant), consider adding atypical antipsychotic (quetiapine, clozapine, olanzapine)
  • Carbamazepine, valproic acid, and lamotrigine do not have good antidepressant effects, they’re only antimanic
  • Tegretol (carbamazepine) not used much because rush of Steven-Johnson’s syndrome, CP450 interactions and neutropenia

Bipolar II

  • MDE + hypomanic episode
  • NO manic or mixed episodes
  • Treatment: lithium, consider adding atypical antipsychotic

Cyclothymia

  • >2 years, never without symptoms for >2 months.
  • Hypomanic + Depressive Symptoms (not meeting the criteria for MDE)
  • Treatment: lithium, anticonvulsants (divalproex, lamotrigine)

 

Substance abuse vs substance dependence

Substance abuse can be generally thought of as a misuse of a substance but with no prominent physiological or psychological tolerance (needing more for the same effect) or withdrawal (negative symptoms when without the substance).

Substance Abuse (DSM IV Criteria)

A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:

  1. Recurrent substance use resulting in a failure to fulfill major obligations at work, school, or home
  2. Recurrent substance use in situations in which it is physically hazardous
  3. Recurrent substance-related legal problems
  4. Continued substance use despite having persistent social or interpersonal problems caused or worsened by the substance

B. Has never met the criteria for Substance Dependence for this class of substance.

Substance Dependence (DSM IV Criteria)

Substance dependence is sort of like the next step. It’s still affecting the person’s life (if not more) but now the person physiologically and/or psychologically needs the substance. You can’t count it as abuse if they have the symptoms of dependence.

A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:

  1. Tolerance, as defined by either of the following:
    • A need for markedly increased amounts of the substance to achieve intoxication or desired effect
    • Markedly diminished effect with continued use of the same amount of the substance
  2. Withdrawal, as manifested by any of the following:
    • The characteristic withdrawal syndrome for the substance (refer to Criteria A and B of the criteria sets for Withdrawal from the specific substances)
    • The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
  3. The substance is often taken in larger amounts or over a longer period than was intended
  4. There is a persistent desire or unsuccessful efforts to cut down or control substance use
  5. A great deal of time is spent in activities necessary to obtaining, using or recovering from the substance
  6. Important activities are given up or reduced because of substance use.
  7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance
Mnemonic for substance dependence: The 3 Cs
  1. Compulsive use
  2. Loss of Control
  3. Consequences of use

Note: for polysubstance dependence a person meets the criteria for dependence and is using 3 or more substances. There is no polysubstance abuse (it is assumed that if you’re using more than 3, you’re dependent).

DSM Criteria for Delirium

Delirium, not to be confused with dementia.

The DSM criteria for delirium:

  1. Disturbance of consciousness
  2. Change in cognition
  3. Develops over a short period of time (hours to days) and fluctuates
  4. There is an identifiable general medical condition (or is substance induced)

It is important to recognize a delirium so that the underlying condition can be treated. It is also important because the delirium itself can be harmful to the patient, for example if someone who is delirious walks out into the cold with only a housecoat.

The longer one has delirium, the longer is takes to resolves, even after the underlying condition is treated.

If someone asks you to asses the level of competency of a person with delirium, it’s best to defer. Competency is both TIME- and QUESTION-dependent, so if you are asking someone when they are lucid, they could still be deemed competent, even if they are likely going to return to being delirious.

Mnemonic for delirium: I WATCH DEATH

  1. Infectious: UTIs, pneumonia, meningitis
  2. Withdrawal: alcohol, benzos
  3. Acute metabolic: liver or kidney failure, electrolytes
  4. Trauma: post-op, head injury
  5. CNS pathology: tumor, stroke, seizure
  6. Hypoxia: anemia, PE, heart failure
  7. Deficiencies in vitamins: thiamine, B12, folate
  8. Endocrine: Glucose, thyroid, adrenal, parathyroid (hypercalcemia)
  9. Acute vascular: shock, hypertensive ecephalopathy
  10. Toxins: alcohol, benzos, anticholinergics, opioids, anesthetics, anticonvulsants, dopaminergic agents, steroids, insulin, antibiotics (quinolines), NSAIDs
  11. Heavy metals: lead, arsenic, mercury

Work up

Standard

  1. CBC, BUN, Creatinine
  2. Extended electrolytes (Na, K, HCO3, Ca, PO, Mg)
  3. Glucose
  4. Liver function tests
  5. Albumin
  6. Urine culture
  7. TSH
  8. Vitamin B12 & folate

And maybe

  • ECG
  • CXR
  • Blood cultures
  • CT head
  • Heavy metal screen
  • VDRL, HIV
  • Lumbar puncture
  • EEG

But I want to earn the radiologist tons of money…
Only if they have:

  • Focal neurological deficit
  • Acute change in status
  • Anticoagulant use
  • Acute incontinence
  • Gait abnormality
  • History of cancer

Parkinson’s Disease

Parkinson’s Disease is a degenerative movement disorder resulting from the death of the dopaminergic neurons in the substantia nigra.

There aren’t any definitive blood tests or imaging for Parkinson’s, so it really comes down to a solid neurological examination.

Generally bradykinesia (slow movement) plus one of the other two cardinal signs

  1. Rigidity (cogwheel)
  2. Tremor (pill rolling)

The other movement signs seen in Parkinson’s

  1. Shuffling gait
  2. Mask-like expression
  3. Postural instability: this is tested with the “pull test” – the examiner stands behind the patient and firmly pulls the patient by the shoulders. Someone with normal postural reflexes should only need to take one step back, someone with postural instability will fall or need to take multiple steps backwards.

Differentiating types of psychosis

Note: my example of a non-bizarre delusion can also be classified as an idea of reference (in which you think that TV or songs are talking about you)

Many psychiatric and general medical conditions can have symptoms of psychosis and mood disorders. The way to figure them out is to look at the timeline and the onset of the psychotic vs. mood symptoms (which came first, are they always at the same time, was there something else going on)

Disorder Duration Psychotic Symptoms Mood Disorder
Schizophrenia More than 1 month of symptoms, disturbance persisting for more than 6 months Present (delusions, hallucinations) Brief duration of mood symptoms
Schizoaffective Disorder Same as schizophrenia Present all along (with and in the absence of a mood disorder) Brief and only at time of psychotic symptoms
Mood Disorder with Psychotic Features Meeting the criteria for depression or bipolar I/II Only at time of mood disorder Present in the absence of psychotic symptoms
Schizophreniform Disorder More than 1 month of symptoms, disturbance persisting less than 6 months Present Brief duration of mood symptoms
Substance-Induced Psychosis During or within 1 month of intoxication or withdrawal (longer implies underlying psychotic disorder) Prominent hallucinations or delusions May exist concurrently
Delusional Disorder At least 1 month Non-bizarre delusions (has never met criterion A in DSM for schizophrenia) Brief in relation to the duration of delusional period

*Brief psychotic disorder: symptoms more than 1 day, less than 1 month and not better accounted for by another psychotic disorder

Toxidromes

toxidromes

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A toxidrome is a syndrome (set of symptoms) caused by specific medications or toxins.

There are 5 big ones to know:

  1. Anticholinergic: low potency antipsychotics, oxybutynin, ACh receptor antagonists (ipratropium, atropine, scopolamine)
  2. Cholinergic: ACh recptor agonists (pilocarpine), AChEIs (organophosphates, phyostigmine)
  3. Opioid: Morphine, heroin, hydromorphone, etc
  4. Sympathomimetic: epinephrine, cocaine, amphetamine (Aderol), methylphenidate (Ritalin)
  5. Sedative-Hypnotic: Benzodiazepines, barbituates, “Z-drugs” (zopiclone, zolpidem), antihistamines
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