Medications Part 4 – Atypical Antipsychotics Aren’t Just for Schizophrenia

A lot of people hear the word “antipsychotic” and shy away from the medication, or think they’re doomed. But in fact, atypical antipsychotics are quite useful in the treatment of bipolar disorder and depression.

 A few are even FDA approved for the use of either augmenting an antidepressant for someone with clinical or major depressive disorder, or as a mood stabilizer for bipolar disorder. I’ve been on atypical antipsychotics since I was 18, and must say, they have less side effects than the first generation ones, and they’re much more helpful. One, called Symbyax, is a pill of Zyprexa and Prozac paired for use in major depression and approved for bipolar depression as well.

 The main atypical antipsychotics are Abilify, Saphris, Fanapt, Latuda, Zyprexa, Symbyax, Invega, Seroquel, Risperdal, Geodon/Zeldox and Clozapine*.

 Antipsychotics, unfortunately, have the risk of major weight gain. I gained 40 pounds while on Zyprexa, it seemed to even out when I switched to Abilify. This can be off-putting for many of those prescribed these medications. Geodon, Clozapine and Abilify are considered “weight-neutral”, meaning they do not cause weight gain or loss(1) but your mileage may vary. I lose weight on Geodon.

 I found Risperdal to be a little sedating for a bit. But the big problem with many atypical antipsychotics (or AAP’s, for short) can cause your prolactin (a hormone) to go up. This, in females, can stop your period and cause “leaky breasts”. It’s not as much fun as it sounds, it’s downright gross and embarrassing to try to explain to your 70 year old shrink that your tits are leaking! Before I took Risperdal, I actually had to take medications to increase my prolactin levels, and I was taken off them before starting Risperdal.

 I find Risperdal to be a good “once in a while” medication. It doesn’t have the mood stabilizing effects that a lot of the others do. It helped with my irritability, but I’ve never been on it long enough to see it’s full effects. But my boobs went from a C to a DD. It is also available in a long acting injection. I don’t like long acting injections because once its in your system, it stays there, and until its completely out, you get the side effects.

 Saphris is a newer AAP and is not available in Canada, to my knowledge, and when swallowed, is only 10% effective, so, like Zyprexa Zydis, it has to be dissolved under the tongue. Reports say that it’s horribly disgusting tasting but it works. You also get a numb mouth for a little bit, which is always heaps of fun. Zyprexa Zydis doesn’t cause as much weight gain as Zyprexa itself, for some reason, and is good at knocking you right out, but there’s always that chalky feeling in your mouth the next day. Ick.

 Seroquel is one of the most well known AAP’s out there and is also known for causing a lot of weight gain. I never really gained on Seroquel, to be honest, and it made me stop smoking so much for some strange reason. Unfortunately I had weird side effects from it (heart arrythmia’s and trouble swallowing) so I had to stop taking it. At one point I was taking 900mg a day, enough to sedate a horse. No wonder I kept falling asleep in class! The dose I’ve noticed most people take is 300-600mg a day, usually at bedtime. It’s good in tiny doses (12.5mg, 25mg) for anxiety or a PRN (as needed) medication. It is also approved to be used with an antidepressant in bipolar and unipolar depression. Some people call it Slurrrroquel because of its sedating effects. It can be used as a mood stabilizer without a combination of an anti-convulsant.

 Geodon is one of my favourites, I honestly shouldn’t have switched to Abilify. Some people find Geodon (called Zeldox in most of the world, I’m using the USA name) very sedating, but I found it not-so-much. I often have trouble sleeping or staying asleep on it. It works as a mood stabilizer as well. It’s weight neutral but can cause akithasia, inner restlessness, something I’m feeling now due to Abilify. Abilify is considered a third generation antipsychotic, while the rest are second generations.

 Okay, this isn’t a review on AAP’s, so I’ll continue on with how they work, how they differ from “typical” antipsychotics and side effects.

 How do they work?

Like most psychiatric medication, they don’t really know how or why they work.(2) The theory is that they act on dopamine (a neurotransmitter) and block other neuroreceptors. Rispderal is said to block the creation of serotonin and dopamine, so the symptoms don’t show up, and Invega works the same way. Zyprexa, Seroquel and Clozapine block several receptors and try to fix the chemical imbalance in the brain, but unfortunately, do to this specific mechanism, type 2 diabetes is a possible side effect, as is weight gain. Abilify is unknown and Geodon is completely different, helping with positive and negative symptoms of schizophrenia, making it a good mood stabilizer.

 Side Effects

They say side effects only occur in 10% of those taking these meds(3) but honestly, I think its much more than that. Common side effects are: weight gain, tachycardia, insomnia, akathisia, agitation, anxiety, headache. It’s kind of funny because some of those side effects are what those medications treat.

 Rare side effects include: Dystonia(4), Parkinsonism(5), tardive dyskenesia and neuroleptic malignant syndrome, and sometimes type 2 diabetes.

 Atypical vs. Typical

Typical antipsychotics are sometimes called neurloeptics because it means “seize the neuron”(6) They tend to control symptoms such as mania, delusions and hallucinations, also called “positive symptoms”. (Do remember, that schizophrenia and bipolar work similarly in the brain) Side effects are similar, but worse, and can cause tardive dyskenesia (7), sometimes they are paired with medications like Cogentin to stop this.

 Though typical’s can treat positive symptoms, the negative symptoms are still there. In the 1980’s, researchers found a way to treat both sides of the spectrum, called atypical antipsychotics, that work on more receptors and have less severe side effects.

 “Researchers speculate that traditional antipsychotic medications completely block one kind of dopamine receptor, leaving other types of dopamine receptors unaffected. Atypical antipsychotics appear to block many kinds of dopamine receptors less completely.”

 

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Nicotine and Glutamate in Bipolar Patients

Glutamate
Many of us are aware that the chemicals and neurotransmitters, dopamine and serotonin play a big role in the brain, affecting moods and thoughts. Too little serotonin, and you get depression. Too much dopamine (a neurotransmitter) and you get mania, and often, hallucinations. An example of an excess of dopamine is in the high you get during use of cocaine or methamphetamine, two things someone whom is bipolar should never use!
 
Glutamate has recently been found to be in excess in the brains of bipolar patients. Glutamate is a neurotransmitter, like dopamine, and is necessary in memory and learning.Genetic and other abnormalities have been found in people with bipolar disorder. Glutamate, to be put more simply, is an amino acid which acts as a messenger for nerve cells. It bonds to a neuron and tells it when to shoot off neurons2. With people with bipolar disorder, it doesn’t function properly, there is often too much glutamine in a manic or mixed episode.
 
Nicotine
It’s no myth that mentally ill folks smoke more than the non-mentally ill. A study by The Journal of the American Medical Association reported that 44.3% of all cigarettes in America are consumed by individuals who live with mental illness and/or substance abuse disorders. This means that people living with mental illness are about twice as likely to smoke as other persons.Withdrawal from nicotine in the mentally ill can sometimes lead to excess depression and anxiety. Findings show that smoking in the mentally ill have an underlying biological etiology3.
 
Nicotine administration normalizes several sensory-processing deficits seen in bipolar disorder and schizophrenia4. Most studies have been done with schizophrenics, but there is are phenotypes5 that suggest bipolar disorder and schizophrenia are linked to a gene defect.
 

From a brain-based perspective, research is being done to determine if and how nicotine is involved in some of the brain’s memory functions. If nicotine is a factor, then this could explain why so many people living with an illness like schizophrenia or other illness involving cognitive deficits may smoke. Even though smoking is thought to enhance concentration and cognition, the effects are short in duration. It is known that people diagnosed with schizophrenia often smoke before the onset of symptoms and that they smoke more often and inhale more deeply than smokers without schizophrenia.6

 

Smoking is often a form of self medication. I quit last May, 2012, and I still find myself reaching for a cigarette when I’m stressed out, anxious, or angry. I definitely agree in studies that say its a form of self medication. Quitting cold turkey (I had an e-cig but it pooped out on me) sucked, and I slept, for literally three days, due to the stimulant effect of nicotine. I still have cravings which come and go with my moods.
 
Nicotine does, however, increase psychotic symptoms because it can cause antipsychotics to be flushed out of the system more quickly, due to the effects smoking has on the kidneys6. Nicotine can act either as a stimulant or a depressant depending on dose and history of use. Today, scientists are researching nicotine receptors in the central nervous system. The reason why many depressed people feel better after smoking a cigarette is that they are correcting a chemical imbalance altered temporarily by nicotine7.
 
Nicotine and GABA
First, what is GABA? We’ve heard a lot about it. I’ve taken this quote to explain:
 
“GABA is the communications speed controller, making sure all brain communications are operating at the right speed and with the correct intensity”, writes Joseph M. Carver, Clinical Psychologist. When there is too little GABA, we become overstimulated and engage in excessive and impulsive behavior. When there is too much GABA, we become overly relaxed and sedated. The levels of GABA are low in schizophrenia and bipolar disorder as well as in epilepsy and other seizure disorders.”
 
The effects of nicotine on GABA are quite profound: GABA rises 10% after smoking a nicotine inhaler, and 45 minutes later, the brain was producting GABA 4x’s faster than an average, non-smoker brain. GABA acts as an inhibitor in the hippocampus part of the brain, slowing the firing of neurons8.
 
How does this relate to bipolar disorder though?
The increase of GABA acts as a mood stabilizer, temporarily and can reduce anxiety. Smoking has negative effects on mania due to serotonin, though. Depending on the current mood, the nicotine could have a negative, or paradoxical effect on your mood. Nicotine can sedate and calm, but prolong mania, due to serotonin levels. Interesting stuff!
 
Glutamate and Nicotine
“Nicotine affects glutamate in the brain and may be one reason why so many people with a mental illness smoke.1
 
 
  1. Common familial or genetic risk or underlying neurophysiology.
  2. The observable physical or biochemical characteristics of an organism, as determined by both genetic makeup and environmental influences