Antipsychotic Seroquel

Dear friend,

The mind …… what a vast ocean of knowledge, pun intended. The mind can be so, so complicated. Controlling one’s mind is probably the most difficult task in the world. I hear Tiger Woods has tremendous mind control and focus. I know that contributes to his being probably the best golfer in the world.

The mind …..posing some philosophical questions. Where does the mind begin? Where does it end? Is it limited to the brain? Does it extend to the body? Does it extend beyond the mind and body? What about consciousness? What is consciousness? Is that chemistry? Physics? Metaphysics? No, I won’t get into all that ….. these are answers each of us finds on our own.

Alright ….. pulling myself back down to earth …. from a totally practical perspective, there are so many stimuli that are fed to the mind. Each of us has such varied responses to the same stimuli, partly dependent on our conditioning from years past. Every one of us has varying degrees of activity of different neurotransmitters in our central and peripheral nervous systems ….. some of it balanced, others unbalanced. When, for whatever reason, there is an imbalance of neurotransmitters in the brain, a combination of wise psychiatric counsel and medication can improve the quality of life.

Quetiapine (pronounced kwe-tie-a-peen) is sold under the brand name Seroquel. It is the most commonly prescribed antipsychotic drug in America. Psychosis is “osis” of the “psyche” (Greek origin) – literally, abnormal condition of the mind. Seroquel was introduced in 1997 as a treatment for schizophrenia.

In schizophrenia (from Greek “schizein” = to split, “phren” = mind), there is increased activity of neurotransmitter dopamine in one of the major dopamine pathways in the brain called mesolimbic pathway. This pathway is involved with emotions of motivation and re-inforcement. The exact mechanism of action of Seroquel is not known, but it is proposed that its primary effect is from antagonism of a type of dopamine receptor D2 and a type of serotonin receptor 5-HT2.  Dopamine and serotonin are neurotransmitters. Dopamine is involved in motor activity, cognition, motivation and reward, sleep, mood, attention and learning. Serotonin modulates sleep, sexuality, anger, aggression, body temperature, mood and appetite.

In addition, Seroquel is metabolized to the active metabolite norquetiapine. In non-human subjects (primates), norquetiapine was shown to inhibit norepinephrine transporter (NET). First of all, what is norepinephrine? Norepinephrine, also called noradrenaline, is a relative of epinephrine or adrenaline. Norepinephrine is a neurotransmitter that plays a role in attention and focus as well as depression. In fight-flight-fright situations, norepinephrine is also released as a stress hormone, but that’s a different story.

NET, that was referred to above, is a protein that helps the reuptake of the neurotransmitter norepinephrine back into its pre-synaptic storage vesicles (for a detailed description of this kind of re-uptake process, please refer to last week’s article on sertraline).

When norquetiapine inhibits NET, it prevents the re-uptake of norepinephrine. This increases the levels of norepinephrine in specific areas of the brain, which contributes to the anti-depressant effect.

Seroquel is also used in the treatment of bipolar disorder. Bipolar disorder is characterized by depressive and manic phases. Seroquel is useful in the depressive episodes. It is used alone, or in combination with lithium or Depakote (divalproex). The combination therapy is useful because lithium and Depakote are particularly useful in stabilizing mood in the manic phases of bipolar disorder.

Off-label uses of Seroquel include Tourette’s syndrome (a tic disorder characterized by involuntary movements and verbal utterances), autism, alcoholism, restless legs syndrome, obsessive-compulsive disorder and post-traumatic stress disorder (PTSD). Speaking of PTSD, check out http://dayofthedoc.blogspot.com – well-written scientific blog on November 11, 2008 (Veteran’s Day).

Seroquel has also been used as a sedative for sleep and anxiety disorders. Antagonism of the histamine H1 receptor has been proposed for the sedative effect of the drug. Yes, histamine is another neurotransmitter.

Sedation is a side-effect of Seroquel when it is not used for that purpose. Orthostatic hypotension (drop in blood pressure when you suddenly stand) is another side-effect mediated by antagonism of adrenergic alpha1 receptors. Weight gain can be a significant side-effect. There have been claims that the use of this medication can lead to diabetes. Tardive dyskinesia – uncontrollable movements of the face, tongue or other parts of the body – is a possible side-effect. Rarely, use of the drug can lead to neuroleptic malignant syndrome. This is characterized by muscle rigidity, fever, unstable blood pressure and delirium possibly leading to coma. The enzyme creatine phosphokinase (CPK) levels are raised due to high muscle activity – this enzyme is a product of muscle breakdown. If this happens, the drug is to be stopped immediately and supportive treatment given – circulatory and ventilatory, sometimes in intensive care.

Seroquel has addiction potential. “Suzie-Q” is its street name. It’s also been called “quell”. It has been snorted, injected intravenously sometimes with cocaine, and used as a “downer” to come off cocaine or amphetamine.

Let’s make a transition from the streets of society to the corridors of power in the world. Is it possible that some of the villainous leaders of history could have been psychotic? Hmmm …. could antipsychotic drugs have prevented some genocides? Who knows? Just some food for thought.

Until next week, please take care of yourself and your health.

Dr. Ajit Damodaran