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Atypical Antipsychotics, or SGAs

Zyprexa

Zyprexa 10mg

AKA: Second-Generation, Atypical Antipsychotics, or simply SGAs.

As mentioned in a previous post, these medications tend to be superior to that of Typical Antipsychotics because they treat BOTH positive and negative symptoms of Schizophrenia Spectrum Disorders.

Q: What the heck are positive vs. negative symptoms of Schizophrenia?

A: Simply put, positive symptoms are psychotic behaviors like:

  • Delusions and paranoia
  • Disordered thoughts and speech
  • Tactile, auditory, visual, olfactory and/or gustatory hallucinations

While negative symptoms are disruptions to normal behaviors and emotions and can sometimes be confused with clinical depression, with symptoms like:

  • Flat, or dull affect (showing no emotion, monotone voice)
  • Lack of pleasure in everyday life
  • Lack of ability to begin and sustain planned activities
  • Speaking little, even when forced to interact


Since both negative and positive symptoms exist within Schizophrenia, the newer, Atypical Antipsychotics are the treatment of choice, here is a list:

  • Aripiprazole (Abilify)
  • Asenapine Maleate (Saphris)
  • Clozapine (Clozaril)
  • Iloperidone (Fanapt)
  • Lurasidone (Latuda)
  • Olanzapine (Zyprexa)
  • Olanzapine/Fluoxetine (Symbyax)
  • Paliperidone (Invega)
  • Quetiapine (Seroquel)
  • Risperidone (Risperdal)
  • Ziprasidone (Geodon)

Common Side Effects:

  • Dry mouth
  • Blurred vision
  • Constipation
  • Dizziness or lightheadedness
  • Weight gain

Sometimes atypical antipsychotics can cause:

  • Problems sleeping
  • Extreme tiredness and weakness. 

With long-term use, atypical antipsychotics can also carry a risk of:

  • Tardive dyskinesia

Though atypical antipsychotics are usually given for Schizophrenia Spectrum Disorders, they have become increasingly popular as an adjunct (or in addition) to an SSRI, or antidepressant. In fact the FDA recently approved Abilify for people who do not respond to antidepressants alone. You’ve all seen the commercials where the Antidepressant and Abilify become friends…?

Abilify

Abilify as an adjunct

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Typical Antipsychotics

AKA: First-Generation, Conventional, or Traditional Antipsychotics, Classical Neuroleptics,or Major Tranquilizers. This class of medications is most often utilized in the treatment of psychotic (positive) symptoms during the course of Schizophrenia.

Here is a list of First-Generation Antipsychotics organized by potency:

Low Potency:

  • Chlorpromazine (Thorazine)
  • Chlorprothixene (Taractan)
  • Levomepromazine (Levoprome)
  • Mesoridazine (Serentil)
  • Thioridazine (Mellaril)

Medium Potency:

  • Loxapine (Loxitane)
  • Molindone (Moban)
  • Perphenazine (Trilafon)
  • Thiothixene (Navane) 

High Potency:

  • Droperidol (Inapsine)
  • Flupentixol (Fluanxol)
  • Fluphenazine (Permitil, or Prolixin)
  • Haloperidol (Haldol)
  • Pimozide (Orap)
  • Prochlorperazine (Compro)
  • Trifluoperazine (Stelazine)


Common Side Effects:

  • Extrapyramidal Symptoms (EPS) like:
    • Acute dystonic reactions: muscular spasms of neck (torticollis,) eyes (oculogyric crisis,) tongue, or jaw
    • Akathisia: A feeling of motor restlessness
    • Pseudoparkinsonism: drug-induced parkinsonism (cogwheel rigidity, bradykinesia/akinesia, resting tremor, and postural instability.
    • Tardive dyskinesia: involuntary asymmetrical movements of the muscles, this is a long term chronic condition associated with long term use of antipsychotics and is sometimes irreversible even with cessation of medication.

Anticholinergic medications are used to treat EPS:

  • Anti-Muscarinic agents
    • Atropine
    • Benztropine (Cogentin)
    • Biperiden
    • Chlorpheniramine (Chlor-Trimeton)
    • Dicyclomine (Dicycloverine)
    • Dimenhydrinate (Dramamine)
    • Diphenhydramine (Benadryl, Sominex, Advil PM, etc.)
    • Doxylamine (Unisom)
    • Glycopyrrolate (Robinul)
    • Ipratropium (Atrovent)
    • Orphenadrine
    • Oxitropium (Oxivent)
    • Oxybutynin (Ditropan, Driptane, Lyrinel XL)
    • Tolterodine (Detrol, Detrusitol)
    • Tiotropium (Spiriva)
    • Trihexyphenidyl
    • Scopolamine
    • Solifenacin
  • Anti-Nicotinic agents
    • Bupropion (Zyban, Wellbutrin) – Ganglion blocker
    • Dextromethorphan – Cough suppressant and ganglion blocker
    • Doxacurium – Nondeplorizing skeletal muscular relaxant
    • Hexamethonium – Ganglion blocker
    • Mecamylamine – Ganglion blocker and occassional smoking cessation aid[2]
    • Tubocurarine – Nondeplorizing skeletal muscular relaxant

Buuuuuuuut, there is such thing as “too much of a good thing” since Anticholinergic medications can cause:

Acute Anticholinergic Syndrome:

  • Ataxia-loss of coordination
  • Decreased mucus production in the nose and throat; consequent dry, sore throat
  • Xerostomia, or dry-mouth with possible acceleration of dental caries
  • Cessation of perspiration; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin
  • Increased body temperature
  • Pupil dilation (mydriasis); consequent sensitivity to bright light (photophobia)
  • Loss of accommodation (loss of focusing ability, blurred vision – cycloplegia)
  • Double-vision (diplopia)
  • Increased heart rate (tachycardia)
  • Tendency to be easily startled
  • Urinary retention
  • Diminished bowel movement, sometimes ileus (decreases motility via the vagus nerve)
  • Increased intraocular pressure; dangerous for people with narrow-angle glaucoma
  • Shaking

Possible effects in the central nervous system resemble those associated with delirium, and may include:

  • Confusion
  • Disorientation
  • Agitation
  • Euphoria or dysphoria
  • Respiratory depression
  • Memory problems
  • Inability to concentrate
  • Wandering thoughts; inability to sustain a train of thought
  • Incoherent speech
  • Irritability
  • Mental confusion (brain fog)
  • Wakeful myoclonic jerking
  • Unusual sensitivity to sudden sounds
  • Illogical thinking
  • Photophobia
  • Visual disturbances
    • Periodic flashes of light
    • Periodic changes in visual field
    • Visual snow
    • Restricted or “tunnel vision”
  • Visual, auditory, or other sensory hallucinations
    • Warping or waving of surfaces and edges
    • Textured surfaces
    • “Dancing” lines; “spiders”, insects; form constants
    • Lifelike objects indistinguishable from reality
    • Phantom smoking
    • Hallucinated presence of people not actually there
  • Rarely: seizures, coma, and death
  • Orthostatic hypotension (sudden dropping of systolic blood pressure when standing up suddenly) and significantly increased risk of falls in the elderly population.

**!!GOLDEN NUGGET!!**
A mnemonic for Anticholinergic Syndrome:

  • Hot as a hare (hyperthermia)
  • Blind as a bat (dilated pupils)
  • Dry as a bone (dry skin)
  • Red as a beet (vasodilation)
  • Mad as a hatter (hallucinations/agitation)
  • The bowel and bladder lose their tone and the heart goes on alone (ileus, urinary retention, tachycardia)

The good news is that Acute Anticholinergic Syndrome is completely reversible and subsides once all of the causative agent has been excreted.

  • Physostigmine is a Reversible Cholinergic Agent that can be used in life-threatening cases.
  • Piracetam (and other racetams), α-GPC and choline are known to activate the cholinergic system and alleviate cognitive symptoms caused by extended use of anticholinergic drugs

With all of that going on it is no wonder that most doctors have switched to the Second-Generation, or Atypical Antipsychotics. That’s not to say that the Typicals are not used, at all. It’s just that Atypicals better treated both the positive AND negative symptoms of Schizophrenia Spectrum Disorders.

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