Atypical Antipsychotics, or SGAs

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 as an adjunct

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.

Selective Serotonin Reuptake Inhibitors, or SSRIs

Serotonin Selective Reuptake Inhibitors, or SSRIs:

• Citalopram (Celexa)
  • Initial dose: 20mg/day.
  • Maintenance dose: 20 to 40mg/day.

Celexa

• Escitalopram (Lexapro)
  • Initial dose: 10mg/day.
  • Maintenance dose: 10-20mg/day.

Lexapro

• Fluoxetine (Prozac)
  • Initial dose: 20mg/day.
  • Maintenance dose: 20-60mg/day.

Prozac

• Paroxetine (Paxil, Pexeva, Sarafem)
  • Initial dose: 20mg/day, titrated slowly by 10mg a week.
  • Maintenance dose: 20-50mg/day, as tolerated/needed.

Paxil 20mg

• Sertraline (Zoloft)
  • Initial dose:
  • Maintenance dose:

Zoloft

Common Side Effects:

• Nausea
• Nervousness, agitation or restlessness
• Dizziness
• Reduced sexual desire or difficulty reaching orgasm or inability to maintain an erection (erectile dysfunction)
• Drowsiness
• Insomnia
• Weight gain or loss
• Headache
• Dry mouth
• Vomiting
• Diarrhea

IMPORTANT: Pharmaceutical companies HAVE to list every side effect reported during clinical trails. So, just because a medication lists a certain side effect DOES NOT MEAN YOU will have it. In fact, most people experience very few side effects and with continued use (2 weeks and beyond), most of the initial side effects dissipate, or resolve completely. Additionally, the dosages listed above are FDA approved for treating Depression in an otherwise healthy Adult. For more specific information in treating your symptoms, consult your doctor. 

Tricyclic Antidepressants, or TCAs

Tricyclic Antidepressants, or TCA:
Cyclic antidepressants are named tri (3), or tetra (4), depending on the # of rings in their chemical makeup.
Maprotiline is a Tetracyclic antidepressant because it has 4 rings.

All of the medications listed below are Tricyclic antidepressants:

• Amitriptyline
  • Initial dose:
    25 to 100mg per day in 3 to 4 divided doses or 50 to 100 mg at bedtime.
  • Maintenance dose:
    25 to 150 mg per day in single or 3 to 4 divided doses.

Amitriptyline

• Amoxapine
  • Initial dose:
    50mg 2, or 3x daily.
    Depending on tolerance, the dosage can be increased to 100mg 2, or 3x daily by the end of the 1st week. When an effective dosage is established, the drug may be given in a single dose (nor more than 300mg) at bedtime.
  • Maintenance: 200-300mg/daily. 

Amoxapine

• Desipramine (Norpramin)
  • Initial dose: 75mg/day orally given as a single dose or in divided doses.
  • Maintenance dose: 100-200mg/day.

Desipramine

• Doxepin
  • For Mild Depression:
    Initial dose: 25mg/day in 1 to 3 divided doses.
    Maintenance dose: 25-50mg/day in 1 to 3 divided doses.
  • For Moderate Depression:
    Initial dose: 75mg/day in 1 to 3 divided doses.
    Maintenance dose: 75-150mg/day in 1 to 3 divided doses.
• For Severe Depression:
  Initial dose: 150mg/day in 1 to 3 divided doses.
  Maintenance dose: 150-300mg/day in 1 to 3 divided doses.
  

  Doxepin carton

• Imipramine (Tofranil)
  • Hospitalized Patients:
    Initial dose: 100mg/day given in 3 to 4 divided doses.
    Maximum dose: 300mg/day.
  • Outpatients:
    Initial dose: 75mg/day given in 3 to 4 divided doses.
    Maximum dose: 300mg/day.
  • Intramuscular: Up to 100mg/day in divided doses.

Tofranil 25mg

• Nortriptyline (Pamelor)
  • 25-150 mg/day orally in divided doses or 1 dose.

Nortriptyline

• Protriptyline (Vivactil)
  • 15 -40mg/day divided into 3 or 4 doses, up to 60mg/day, if necessary.

Protriptyline-hydrochloride

• Trimipramine (Surmontil)
  • Outpatients:
    Initial: 75mg/day, orally in divided doses.
    Titration: May increase up to 150mg/day.
    Usual range: 50-150mg/day.
  • Hospitalized patients: 100mg/day, orally in divided doses.
    Titration: May increase gradually over a few days to 200mg/day.
    If there is no improvement after 2 to 3 weeks, the dose may be increased to 250 to 300 mg per day.
    Maximum Dose: 300 mg per day.

Trimipramine

Common Side Effects:

• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Drowsiness
• Increased appetite leading to weight gain
• Drop in blood pressure when moving from sitting to standing, which can cause lightheadedness
• Increased sweating

IMPORTANT: Pharmaceutical companies HAVE to list every side effect reported during clinical trails. So, just because a medication lists a certain side effect DOES NOT MEAN YOU will have it. In fact, most people experience very few side effects and with continued use (2 weeks and beyond), most of the initial side effects dissipate, or resolve completely. Additionally, the dosages listed above are FDA approved for treating Depression in an otherwise healthy Adult. For more specific information in treating your symptoms, consult your doctor. 

**Nearly all of the medications listed above have been replaced by newer antidepressants with less side effects. See my posts on SSRIs and SNRIs **

Serotonin and Norepinephrine Reuptake Inhibitors, or SNRIs

Serotonin and Norepinephrine Reuptake Inhibitors, or SNRIs:

• Duloxetine (Cymbalta)
  • For Depression: Cymbalta should be administered a total dose of 40mg/day (20mg 2x daily) to 60 mg/day (given either 1x daily or 30mg 2x daily). There is no evidence that doses greater than 60mg/day give additional benefits.
  • 20 mg opaque green capsules imprinted with “Lilly 3235 20mg”
  • 30 mg opaque white and blue capsules imprinted with “Lilly 3240 30mg”
  • 60 mg opaque green and blue capsules imprinted with “Lilly 3270 60mg”

Cymbalta 60mg

• Venlafaxine (Effexor XR)
  • Immediate release:
    Initial dose: 37.5 mg orally twice a day or 25 mg orally 3 times a day
    Maintenance dose: May increase in daily increments of up to 75 mg at intervals of no less than 4 days
    Maximum dose: (moderately depressed outpatients): 225 mg/day
    Maximum dose (severely depressed inpatients): 375 mg/day
    Daily dosage may be divided in 2 or 3 doses/day
    Extended release, or XR:
    Initial dose: 75 mg orally once daily
    Maintenance dose: May increase in daily increments of up to 75 mg at intervals of no less than 4 days
    Maximum dose (moderately depressed outpatients): 225 mg/day
    Maximum dose (severely depressed inpatients): 375 mg/day

  • 

    EffexorXR 75 and 150mg

• Desvenlafaxine (Pristiq)
  • 50 mg 1x daily, with or without food.
    

    Pristiq 50mg

Common Side Effects:

• Nausea
• Dry mouth
• Dizziness
• Excessive sweating

Other side effects may include:

• Tiredness
• Difficulty urinating
• Agitation or anxiety
• Constipation
• Insomnia
• Sexual problems, such as reduced sexual desire, difficulty reaching orgasm, or the inability to maintain an erection (erectile dysfunction)
• Headache
• Loss of appetite

IMPORTANT: Pharmaceutical companies HAVE to list every side effect reported during clinical trails. So, just because a medication lists a certain side effect does not mean YOU will get it. In fact, most people experience very few side effects and with continued use (2 weeks and beyond), most of the initial side effects dissipate, or resolve completely.