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Quetiapine (branded as Seroquel, Xeroquel, Ketipinor, Ketilept and Derin) is a short-acting atypical antipsychotic approved for the treatment of schizophrenia, bipolar disorder, and along with an antidepressant to treat major depressive disorder.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
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.
Quetiapine was developed by AstraZeneca from 1992-1996 as an improvement from first-generation antipsychotics. It was first approved by the FDA in 1997.[citation needed]
Recreational usage 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.[1] 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.[1] 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.
Quetiapine was developed by AstraZeneca from 1992-1996 as an improvement from first-generation antipsychotics. It was first approved by the FDA in 1997.[citation needed]
Annual sales of Seroquel are approximately $5.7 billion worldwide, with $2.9 billion in the United States.[2] The U.S. patent,[3] which was set to expire in 2011, received a pediatric exclusivity extension which pushed its expiration to March 26, 2012.[3][4] The patent has already expired in Canada.
There are now several name brand versions of quetiapine, such as Quepin, Seroquel and Ketipinor.[5]
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 adrenergicantagonist, as well as a potent antihistamine with clinically negligible anticholinergic properties.[6][7][8][9] Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors.[10] 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 cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe 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.
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:
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.
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.
Combination effects
Cannabis: Cannabis' effects synergise with quetiapine's effects thus increasing the physical effects of the "high" while decreasing the cognitive effects. [11]
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.[13]
Bipolar disorder: In those with bipolar disorder, quetiapine is used to treat depressive episodes and acute manic episodes associated with bipolar I disorder.[14][15]
Major depressive disorder: Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD).[16][17] However, sedation is often an undesirable side effect.[16]
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.[18][19]
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.[20][21] It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,[22] musical hallucinations[23] and anxiety disorders.[24] 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[25] lawsuits[26][27][28] 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.[29] According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%.[29] Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.[30]
Weight gain can be a problem for some, with quetiapine causing more weight gain than other more commonly used antipsychotics.[31]
Compared to other antipsychotics, quetiapine has been reported to be relatively safer in overdose.[32] 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.[33]
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.[34][35] 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.[36][37]
Dangerous interactions
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Stimulants - It can be dangerous to combine depressants with stimulants due to the risk of accidental excessive intoxication. Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.
Dissociatives - This combination can unpredictably potentiate the amnesia, sedation, motor control loss and delusions that can be caused by each other. It may also result in a sudden loss of consciousness accompanied by a dangerous degree of respiratory depression. If nausea or vomiting occurs before consciousness is lost, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Legal status
Austria: It is available by prescription only and unscheduled.[citation needed]
France: It is available by prescription only and unscheduled.[citation needed]
Germany: Quetiapine is a prescription medicine, according to Anlage 1 AMVV.[38]
Switzerland: Quetiapine is listed as a "Abgabekategorie B" pharmaceutical, which requires a prescription.[citation needed]
United Kingdom: Available by prescription only - unscheduled, but unpopular.[citation needed]
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.[citation needed]
↑Davis, K. L., Neuropsychopharmacology, A. C. of (2002). Neuropsychopharmacology: The Fifth Generation of Progress : an Official Publication of the American College of Neuropsychopharmacology. Lippincott Williams & Wilkins. ISBN9780781728379.
↑Maglione, M., Maher, A. R., Hu, J., Wang, Z., Shanman, R., Shekelle, P. G., Roth, B., Hilton, L., Suttorp, M. J., Ewing, B. A., Motala, A., Perry, T. (2011). Off-Label Use of Atypical Antipsychotics: An Update. AHRQ Comparative Effectiveness Reviews. Agency for Healthcare Research and Quality (US).
