Quetiapine

Summary sheet: Quetiapine

Quetiapine
Chemical Nomenclature
Common names	Quetiapine, Seroquel
Substitutive name	Xeroquel, Ketipinor
Systematic name	2-(2-(4-dibenzo[b,f] [1,4]thiazepine- 11-yl- 1-piperazinyl)ethoxy) ethanol
Class Membership
Psychoactive class	Antipsychotic
Chemical class	Dibenzothiazepine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. Oral Dosage Bioavailability 100% - 100% Threshold 10 - 25 mg Light 25 - 50 mg Common 50 - 150 mg Strong 150 - 300 mg Heavy 300 mg + Duration Total 4 - 8 hours Onset 20 - 40 minutes DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions

Quetiapine (branded as Seroquel, Xeroquel, and Ketipinor) is a short-acting atypical antipsychotic approved for the treatment of schizophrenia, bipolar disorder, and along with an antidepressant to treat major depressive disorder.

Recreational usage of this substance is uncommon, but reports of quetiapine abuse have emerged within the medical literature. This seems to be driven by its sedative and anxiolytic effects (to help with sleep or to 'calm down') rather than by its antipsychotic properties. In addition to oral administration, the drug is sometimes taken intranasally by insufflating pulverized tablets. Some estimate that up to 30% of inmates who were seen for psychiatric services in the Los Angeles County Jail were faking psychotic symptoms in an attempt to obtain quetiapine. It is thought that this drug is more commonly abused in prisons than on the street due to its capacity to be regularly prescribed as a sedative and the unavailability in prison of more commonly abused substances.

Annual sales of Seroquel are approximately $5.7 billion worldwide, with $2.9 billion in the United States. The U.S. patent, which was set to expire in 2011, received a pediatric exclusivity extension which pushed its expiration to March 26, 2012. The patent has already expired in Canada. Quetiapine was developed by AstraZeneca from 1992-1996 as an improvement from first-generation antipsychotics. It was first approved by the FDA in 1997. There are now several name brand versions of quetiapine, such as Quepin, Seroquel and Ketipinor.

Contents

Chemistry

Quetiapine is an atypical antipsychotic drug and dibenzothiazepine derivative. Quetiapine contains a thiazepine ring, a seven-membered ring containing one sulfur and one nitrogen group, located at R₁ and R₄ respectively. This ring is fused to two benzene rings, thus forming a dibenzothiazepine moiety. Dibenzothiazepine is connected at R₁₁ to the nitrogen group of a piperidine ring at R₄.

Piperazine is a six-member unsaturated ring with two nitrogen constituents in the 1,4 positions. This ring is connected at its second nitrogen group to an ethoxyethanol chain. It is connected to R₂ of an ethane chain through an oxygen bridge to an ethanol group. This forms the structure of quetiapine.

It is commonly synthesized by nucleophilic substitution to combine the dibenzothiazepine core with the rest of the structure. Quetiapine is present in its pill form as a fumarate salt.

Pharmacology

Quetiapine is a powerful dopaminergic, serotonergic, and adrenergic antagonist, as well as a potent antihistamine with clinically negligible anticholinergic properties. Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors. In terms of its antipsychotic effects, the precise mechanism of action is unknown, but according to the dopamine theory of schizophrenia, antipsychotic effects might be related to the drug’s ability to reduce dopaminergic neurotransmission within the mesolimbic pathway.

Subjective effects

Disclaimer: The effects listed below are taken from the subjective effect index, which is based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy degree of skepticism. It is worth noting that these effects will rarely (if ever) occur all at once, although higher doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

• • Sedation - In terms of energy level alterations, this drug has the potential to be extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
  • Dizziness
  • Dehydration
  • Motor control loss
  • Headaches
  • Decreased libido
  • Increased blood pressure
  • Appetite enhancement
  • Increased heart rate
  • Orgasm suppression
  • Difficulty urinating

Cognitive effects

• The general headspace of quetiapine is often described as one of sleepiness, emptiness, apathy, stupor, and catatonia. The specific cognitive effects can be broken down into several components which progressively intensify proportional to dosage. The most prominent of these cognitive effects generally include:
  • Thought deceleration
  • Analysis suppression
  • Emotion suppression
  • Creativity suppression
  • Language suppression
  • Focus suppression
  • Anxiety suppression
  • Disinhibition
  • Motivation suppression
  • Amnesia
  • Dream potentiation
  • Sleepiness

After effects

• • Residual sleepiness - While quetiapine can be used as an effective sleep-inducing aid, its effects may persist into the morning afterward, which may lead to users feeling "groggy" or "dull" for up to a few hours.
  • Thought deceleration
  • Thought disorganization
  • Irritability - This effect typically occurs the morning after quetiapine has been taken as a sleep-inducing aid, and only occurs for a few hours upon awakening.

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

• Experience:25mg Quetiapine - Nice buzz

Additional experience reports can be found here:

• Erowid Experience Vaults: Quetiapine

Medical uses

• Schizophrenia: There is tentative evidence of the benefit of quetiapine versus placebo in schizophrenia; however, definitive conclusions are not possible due to the high rate of attrition in trials (greater than 50%) and the lack of data on economic outcomes, social functioning, or quality of life.
• Bipolar disorder: In those with bipolar disorder, quetiapine is used to treat depressive episodes and acute manic episodes associated with bipolar I disorder.
• Major depressive disorder: Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD). However, sedation is often an undesirable side effect.
• Parkinsons disease: Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their very low extrapyramidal side effect liability. Owing to the risks associated with clozapine (e.g., agranulocytosis, diabetes mellitus, etc.), clinicians often attempt treatment with quetiapine first, although the evidence to support quetiapine's use for this indication is significantly weaker than that of clozapine.
• Other: The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects. It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome, musical hallucinations and anxiety disorders. It is particularly useful as a tool for forced sedation during bad trips or prolonged unwanted stimulation.

Toxicity and harm potential

Quetiapine likely has a low toxicity relative to dose. Although simply trying this substance at a low to moderate dosage is considered as quite safe, there is an emerging controversy regarding quetiapine fatalities. Approximately 10,000 lawsuits against AstraZeneca for problems ranging from slurred speech and chronic insomnia to death have been filed by individuals from civilian populations.

Both typical and atypical antipsychotics can cause tardive dyskinesia. According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%. Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.

Weight gain can be a problem for some, with quetiapine causing more weight gain than other more commonly used antipsychotics.

It is strongly recommended that one use harm reduction practices when using this drug.

Lethal dosage

Compared to other antipsychotics, quetiapine has been reported to be relatively safer in overdose. Most instances of acute overdoses result only in sedation, hypotension and tachycardia, but cardiac arrythmia, coma and death have occurred in adults. Quetiapine concentrations within the patients' blood are usually in the 1–10 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases.

Tolerance and addiction potential

Quitiapine is moderately physically and psychologically addictive.

Tolerance will develop to the antipsychotic effects and within a week of continuous use. The tolerance to the amount of sedation will be the most noticeable. After cessation, the tolerance returns to baseline in 7 - 14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.

The addictive qualities of quetiapine have not been formally studied and are largely known through anecdotal sources. For example, a letter to the editor that appeared in the January 2007 American Journal of Psychiatry has proposed a “need for additional studies to explore the addiction-potential of quetiapine”. The letter reports that its authors are physicians who work in the Ohio correctional system. They report that “prisoners have threatened legal action and even suicide when presented with discontinuation of quetiapine” and that they have “not seen similar drug-seeking behavior with other second-generation antipsychotics of comparable efficacy”.

Withdrawal symptoms

Withdrawal symptoms reported to occur after discontinuation of quetiapine and other antipsychotics include nausea, emesis, lightheadedness, diaphoresis, dyskinesia, orthostatic hypotension, tachycardia, insomnia, nervousness, dizziness, headache, excessive non-stop crying, and anxiety. According to Eli Lilly internal documents, discontinuation of atypical neuroleptics similar to seroquel can also cause psoriasis, gingivitis and other inflammatory conditions, dyspepsia, headache, high blood sugar and other health conditions unrelated to psychiatric condition.

Legal issues

• Austria: It is available by prescription only and unscheduled.
• France: It is available by prescription only and unscheduled.
• Germany: Quetiapine is a prescription medicine, according to Anlage 1 AMVV.
• United Kingdom: Available by prescription only - unscheduled, but unpopular.
• United States: Quetiapine (Seroquel) is unscheduled in the United States, but is available by prescription only. This means that sales and distribution are allowed only by those with a license and only to those with a prescription (according to FDA regulations). Possession is not illegal even without a prescription.

See also

• Responsible use
• Depressants
• Antipsychotics

External links

• Quetiapine (Wikipedia)
• Quetiapine (Erowid Vault)
• Quetiapine (TiHKAL / Isomer Design)