paroxetine

AKA

Paxil®, Paxil CR®, Brisdelle, Pexeva, Ag-Paroxetine®, Apo-Paroxetine®, Auro-Paroxetine®, Bio-Paroxetine®, Jamp-Paroxetine®, M-Paroxetine®, Mar-Paroxetine®, Mint-Paroxetine®, NRA-Paroxetine®, PMS-Paroxetine®, Riva-Paroxetine®, Teva-Paroxetine® and others

Purpose [+] Antidepressant, Anxiolytic, Anti-obsessional

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Alcohol

Booze, ethyl or ethanol, adult beverage, brew, brewski, liquor, drink, shot, sauce, rot gut, hooch, giggle juice, moonshine, jello shots, wobbly pop

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Interaction
a) Two studies found little difference in psychomotor impairment in subjects receiving paroxetine alone compared to paroxetine combined with alcohol; the exception being significant reductions in attentiveness and increased reaction times seen with co-administration of alcohol.

b) One study done in elderly subjects found that paroxetine blocked alcohol-induced sedation.

c) A study, involving 56 men, examining the role of the serotonin system in alcohol-related aggression found that co-administration of paroxetine 20 mg reduced these alcohol-related aggressive behaviours.

d) There are many case reports (at least 93; however, many are anecdotal) in which patients treated with SSRIs developed new or worsened alcohol use disorders. These generally resolved once the medication was discontinued. This occurred in patients who drank minimal alcohol before starting an SSRI as well as patients who already had alcohol use disorders.

e) There are at least 100 case reports describing "pathological intoxication" when SSRIs were taken with alcohol. Patients taking relatively small amounts of alcohol (that were tolerated will before SSRI initiation) have lead to unexpectedly gross disinhibition and even violence or suicide. In at least 4 patients, re-exposure to the same drug or a related antidepressant reproduced this finding. 32 of these patients reported an increased or altered pattern of alcohol use after SSRI initiation.

Mechanism
a,b) additive CNS depressant effects.

Lack of potentiation of alcohol effects has been consistently noted with drugs that primarily affect serotonin reuptake (e.g. citalopram and other SSRIs). This class of medications lacks affinity for the histamine H1 receptor, blockade of which is associated with sedation. Many older antidepressant agents (e.g. amitriptyline and other tricyclics) produce strong H1 blockade and show additive CNS effects with alcohol.

Significance
a,b) Paroxetine may cause more sedative effects than some other SSRIs. The additive CNS depressant effects of this combination may impair the ability to drive and to carry out other tasks requiring alertness. Patients should be warned that they may be unaware of the effects.

d) Patients started on paroxetine should be monitored for increased alcohol cravings or consumptions.

e) It is possible that patients initiating SSRI therapy may experience higher levels of intoxication with amounts of alcohol that they previously tolerated.

They should be aware that this may affect their ability to drive or do other activities that require alertness or attention safely.

Serious Risk for Harm

It is possible that taking paroxetine makes it more likely for you to get "drunk" off a smaller amount of alcohol. This means that you may have been able to drink a certain amount before, but now that amount could make it unsafe for you to drive or do other activities that require alertness or attention.

Think First

Mixing paroxetine with alcohol doesn't seem to change the risk of drinking alcohol in moderation. This means your usual dose of paroxetine and 1 or 2 drinks.

Remember, 1 drink = 1 beer, 1 glass of wine or 1 shot of liquor.

Think First

It is possible that paroxetine may make you crave alcohol and drink more than you normally would. If this happens you should tell your doctor, pharmacist, or parents.

If you are depressed, blue, or moody, alcohol is a 'downer' and will make you feel worse.

Tobacco

smokes, butts, cigs, cigars, darts, stogies, cancer sticks, chew, dip

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Interaction
One study found that taking paroxetine for 1 month did not attenuate the increases in blood pressure and heart rate caused by smoking, but further increases in blood pressure caused by stress after smoking were attenuated by paroxetine.

Significance
The authors question whether paroxetine may have cardiovascular benefits when used in smokers and suggest that more research be done in this area.

Unknown Dangers

Unknown dangers.

Caffeine

coffee, java, joe, soda, pop, tea, energy drinks (Red Bull®, Monster®, Rock Star®, Amp®, NOS®, Full Throttle®, 5-hour Energy Drink®, Beaver Buzz®), chocolate, cocoa

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Interaction

A high dose of caffeine (4.8 g) was suggested as a contributing factor in a patient who developed symptoms of serotonin syndrome while also taking paroxetine 20 mg and amoxapine 200 mg.

Mechanism

The authors suggest that large doses of caffeine may promote serotonergic activity.

Significance

The significance of this case report is unclear.

Think First

Taking large amounts of caffeine may cause shaking hands, fast heart beat, trouble sleeping at night, edgy or irritable feelings. If you are taking paroxetine to help with anxiety, this may work against the helpful effects of paroxetine.

Unknown Dangers

Cannabis/ Hash

Marijuana, mary jane, BC bud, blunt, chronic, J, jay, joint, hemp, pot, grass, herb, 420, dope, THC, weed, reefer, ganja, gangster, skunk, hydro, hash oil, weed oil, hash brownies, grease, boom, honey oil, K2, spice, poppers, shatter, budder

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Interaction

a) As a CNS depressant, paroxetine has the potential to enhance the adverse or toxic effects of other CNS depressants such as cannabis.

b) There is a case report of a 15-year-old female who experienced hypotension after co-consuming paroxetine while smoking cannabis. While the interaction was rated as doubtful, an interaction between paroxetine and cannabis may be cautioned.

Mechanism

a) The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

b) Cannabidiol (CBD) inhibits CYP2D6, although this has not yet been proven at doses used in human studies. Paroxetine is a CYP2D6 substrate.

Significance

a) It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

b) Patients taking paroxetine and using cannabis may experience increased adverse effects from paroxetine.

Serious Risk for Harm

Paroxetine can cause sleepiness, dizziness and confusion. Cannabis use can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Think First

Cannabis might slow down the removal of paroxetine from your body. This might give you more side effects from paroxetine.

Think First

For some people, cannabis use can increase feelings of anxiety or cause panic attacks. This is more likely to happen if you have an anxiety disorder or do not use cannabis on a regular basis, and could work against the helpful effects of paroxetine.

Cocaine/ Crack

coke, snow, flake, nose candy, blow, lady white, stardust, rock, crystal, bazooka, moon rock, tar

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Interaction
a) Cocaine use may result in decreased clearance of paroxetine leading to increased serum levels.

b) Concomitant use of cocaine and paroxetine may theoretically lead to development of serotonin syndrome.

c) Concomitant use of paroxetine with cocaine may result in QTc interval prolongation and an arrhythmia with the potential to develop Torsades de Pointes.

Mechanism
a) Cocaine is a strong CYP2D6 inhibitor and can inhibit the metabolism of paroxetine, a CYP2D6 substrate.

b) Cocaine and paroxetine both bind to the serotonin transporter. Cocaine has the ability to block the reuptake of norepinephrine, dopamine, and serotonin.

c) Additive QTc prolongation.

Significance
a) The potential for CYP2D6 inhibition puts patients who are co-administering these two drugs at increased risk of adverse or toxic effects associated with higher levels of paroxetine; however, to what extent cocaine inhibits the metabolism of paroxetine is unclear.

b) Concomitant use of cocaine and paroxetine may theoretically have additive inhibition of serotonin reuptake and could lead to serotonin syndrome.

c) Due to increased risk of QTc interval prolongation, cocaine use should be avoided while taking paroxetine.

Serious Risk for Harm

If you are taking paroxetine, using cocaine may increase the risk for side effects from both drugs and you could get: very high fever, really sick, dangerously high blood pressure, a very fast heart beat, heart problems and even die. This is 'serotonin syndrome'.

Serious Risk for Harm

Use of cocaine with paroxetine could cause your heart to have an abnormal rhythm. This abnormal heart rhythm could make you feel dizzy, pass out, or even kill you.

Serious Risk for Harm

Cocaine slows down the removal of paroxetine from the body. This puts you at risk of increased side effects from paroxetine, or even an overdose of paroxetine.

Opioids

codeine, Tylenol #3®, cody, meperidine, Demerol®, DXM, dextromethorphan, robo, skittles, morphine, morph, monkey, methadone, bupe, sub, or dollies, oxycodone, Oxycontin®, hillbilly heroin, OxyNeo®, OC, oxy, roxy, percs, fentanyl, Sublimaze®, Duragesic®, china white, hydrocodone, Hycodan®, Vicodin®, suboxone®, buprenorphine, vike, heroin, H, horse, junk, smack, brown sugar, black tar, down, china white, purple drank, W18, carfentanil, elephant tranquilizer, loperamide, lope, lean

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Interaction

ALL OPIOIDS: a) As a CNS depressant, paroxetine has the potential to enhance the adverse or toxic effects of other CNS depressants such as opioids.

CODEINE: Codeine may not provide effective analgesia when taken in combination with paroxetine.

DEXTROMETHORPHAN: a) Inhibition of dextromethorphan metabolism by paroxetine is well established.

b) Two case reports describe patients developing serotonin syndrome after taking paroxetine and dextromethorphan together.

FENTANYL: 3 case reports describes patients taking paroxetine who experienced serotonin syndrome or toxicity after starting fentanyl. Symptoms resolved when both medications were stopped.

HYDROCODONE: Maximum plasma concentration, half-life, and AUC of hydrocodone was not altered by paroxetine.

Maximum plasma concentration and AUC of hydromorphone (minor active metabolite) was decreased.

HYDROMORPHONE: An 81 year old woman who took related drug fluoxetine 20 mg daily and other medications for several years developed abnormal movements, confusion, incoherent speech, sweating, redness, tremor, hyperreflexia and muscle spasm 2 days after starting hydromorphone 12 mg daily. Fluoxetine was stopped and the symptoms resolved.

LOPERAMIDE: QTc prolongation has been observed with paroxetine. Concomitant use with high-dose loperamide (>100 mg/day) may result in an arrhythmia with the potential to develop Torsades de Pointes.

MEPERIDINE: a) A case report describes a 44 year old woman taking related drug citalopram 20 mg daily increased to 40 mg daily, transdermal fentanyl, IV hydromorphone or oral hydrocodone/acetaminophen PRN, promethazine, gatifloxacin, zolpidem, and lansoprazole developed symptoms of serotonin syndrome within 10 hours of starting meperidine PRN via patient controlled analgesia (PCA). The total dose of meperidine was 230 mg over 8 hours. Meperidine was stopped and the symptoms resolved.

METHADONE: a) Methadone may decrease the metabolism of paroxetine.

b) In a study of 10 patients with narcotic dependence receiving methadone maintenance therapy (8 extensive CYP2D6 metabolizers and 2 poor CYP2D6 metabolizers), co-administration of paroxetine 20 mg resulted in a 35% increase in steady-state methadone levels. In extensive metabolizers, both R- and S-methadone levels increased, but only S-methadone levels increased in poor metabolizers. With the exception of one patient reporting feeling high the first night after paroxetine initiation, no symptoms of toxicity or over-medication were reported.

c) QTc interval prolongation has been observed with paroxetine, thus concomitant use with methadone may result in an arrhythmia with the potential to develop Torsades de Pointes.

MORPHINE:A patient, who had been taking paroxetine prior to surgery, was given morphine and ondansetron during the surgery. She experienced post-operative delirium (agitation, confusion, uncontrolled limb movements, abnormal ocular function, hypertension, pyrexia, brisk reflexes, ankle clonus, elevated creatinine phosphokinase (CPK)) during the following 2 days.

OXYCODONE: a) 20 CYP2D6 extensive or ultrarapid metabolizers taking oxycodone were given paroxetine 20 mg daily for 7 days. The AUC of oxycodone was increased by 19%. The AUC of the metabolite noroxycodone was increased 2-fold, while the AUC of the metabolite oxymorphone was decreased by 67%. Use of rescue analgesia or oxycodone efficacy was not altered. 2 placebo controlled studies showed that paroxetine decreased the AUC of oxymorphone by 44-66% and increased the AUC of noroxycodone by 68-70% but had no effect on pain scores.

b)12 healthy subjects given paroxetine 20 mg daily for 3 doses had no change in the pharmacokinetics of a single dose of oxycodone or noroxycodone, but the maximum concentration of oxymorphone was decreased by 38%. Unlike the other studies, in this study pre-treatment with paroxetine decreased miosis and oxycodone analgesia.

c) Symptoms of serotonin syndrome occurred in a patient taking related drug escitalopram and extended release oxycodone after the oxycodone dose was increased.

d) A cohort study of adults who initiated oxycodone while on SSRI therapy found that the adjusted incidence rate of opioid overdose was higher in patients using CYP2D6-inhibiting SSRIs, such as paroxetine (9.47 per 1000 person-years), compared with those using other SSRIs (7.66 per 1000 person-years). This corresponded to an adjusted hazard ratio of 1.23 (95% CI, 1.06–1.31), indicating an increased risk of overdose with concomitant use of CYP2D6-inhibiting SSRIs.

TRAMADOL: a) A potential risk for serotonin syndrome exists due to tramadol also causing blockade of serotonin reuptake. In addition, an increase in seizure risk was noted by the manufacturer of tramadol when used with SSRIs.

b) A man taking paroxetine 20 mg daily developed symptoms of serotonin syndrome (shivering, diaphoresis, myoclonus) and became subcomatose 12 hours after receiving a 100 mg dose of tramadol. Tramadol was discontinued and his paroxetine dose was reduced by 50%; symptoms resolved over the following week.

c) 3 days after initiating tramadol 50 mg three times daily, a 78-year-old woman taking paroxetine 20 mg daily developed nausea, diaphoresis, and irritability. Her condition worsened the following day and she developed muscular weakness, confusion, pyrexia, and tachycardia. Both drugs were withdrawn and her symptoms resolved. Paroxetine was later restarted with no problems.

d) A similar interaction was seen in another elderly woman, taking paroxetine 10 mg daily, 2 days after tramadol 50 mg four times daily was initiated.

e) 56 days after starting treatment with tramadol, paroxetine, and doxepin, a patient with tetraparesis and chronic pain experienced nightmares and hallucinations. Symptoms resolved only after discontinuation of medications.

f) In a placebo-controlled study of 16 healthy subjects pre-treated with paroxetine 20 mg daily for 3 days, investigators saw a 35% increase in tramadol AUC and a 40-67% decrease in the AUC of the O-demethylated metabolites. The analgesic effect of tramadol was also diminished. Another study found a similar, dose-dependent reduction in the production of (+)-O-desmethyltramadol when patients were given tramadol and paroxetine.

g) A 53-year-old patient developed serotonin syndrome and mania dung treatment with paroxetine and tramadol. This patient decided to increase the paroxetine and tramadol dosage to four tablets per day due to worsening pain. The manic symptoms persisted even after the resolution of the other symptoms of serotonin syndrome after one week.

OTHER OPIOIDS: a) The serotonergic effects of SSRIs may be enhanced by concomitant use with serotonergic opioids.

b) Concomitant use of paroxetine and opioids increase patient risk of secondary constipation, potentially leading to hemorrhoids, rectal prolapse, and fecal impaction.

Mechanism

ALL OPIOIDS: a) The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

CODEINE: Reduced codeine efficacy is due to reduced formation of the active metabolite opioid agonist (morphine) via CYP2D6 due to strong CYP2D6 inhibition by paroxetine.

DEXTROMETHORPHAN: a) Paroxetine inhibits CYP2D6 which metabolizes dextromethorphan.

b) Serotonin syndrome is a dose-related response to the use of serotonergic drugs, often in combination. Genetic polymorphism in CYP2D6 function leads to differences in the ability to metabolize dextromethorphan which may explain the differences in clinical experiences reported by those who abuse dextromethorphan for its dissociative effects.

FENTANYL, HYDROMORPHONE, MEPERIDINE: Additive serotonergic effects could contribute to an increased risk of serotonin syndrome.

LOPERAMIDE: Both paroxetine and high dose loperamide can cause QTc interval prolongation. When used together, these effects may be additive.

METHADONE: a) Both methadone and paroxetine have been identified as a moderate inhibitors of the CYP2D6 enzymatic pathway. Paroxetine is also a CYP2D6 substrate.

c) Paroxetine and methadone are both QTc prolonging agents.

OXYCODONE: Paroxetine inhibits CYP2D6 which reduces metabolism of oxycodone to oxymorphone.

TRAMADOL: a) Additive serotonergic effects could contribute to an increased risk of serotonin syndrome.

Tramadol can cause seizures, and SSRIs can lower the seizure threshold.

Paroxetine is a strong CYP2D6 inhibitor. This can lead to decreased metabolism of tramadol to the active metabolite with analgesic activity.

Paroxetine is also a mild inhibitor of CYP1A2, CYP2C9, CYP2C19, and CYP3A4 and this may explain the differences seen between poor and extensive metabolizers.

OTHER OPIOIDS:a) Additive serotonergic effects.

b) Decreased smooth-muscle contractility through paroxetine anticholinergic effects, combined with reduced peristalsis, increased anal sphincter tone, and reduced defecation response through stimulation of mu and delta opioid receptors.

Significance

ALL OPIOIDS: a) It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

CODEINE: Codeine may not be the best choice for analgesic therapy in patients currently maintained on paroxetine due to its potential to reduce the analgesic effect of codeine.

DEXTROMETHORPHAN: a) This interaction appears to affect extensive CYP2D6 metabolizers (the most common phenotype) only.

b) If therapeutic doses of dextromethorphan and an SSRI are enough to elicit serotonin syndrome, then the combination of these drugs should be avoided. One case study suggests that supra-therapeutic doses of dextromethorphan are a risk factor for the development of serotonin syndrome.

HYDROCODONE: Hydrocodone can be administered with paroxetine without dose modification.

LOPERAMIDE:Due to increased risk of QTc interval prolongation, it is recommended to avoid concomitant use of high-dose loperamide (>100 mg/day) and paroxetine.

METHADONE: a,b) Although co-administration of paroxetine and methadone does not appear to result in increased toxicity, caution is advised as information regarding this interaction is limited. Patients should be monitored during any dosage adjustments.

c) Due to increased risk of QTc interval prolongation, caution is recommended with concomitant use of methadone and paroxetine.

OXYCODONE: Overall, analgesic efficacy of oxycodone was not generally reduced by paroxetine.

d) Concomitant use is more likely to enhance the adverse and toxic effects of oxycodone. Patients should be closely monitored for signs of adverse effects.

TRAMADOL: Tramadol may not be the best choice for analgesic therapy in patients currently maintained on paroxetine due to the potential for paroxetine to reduce the analgesic effects of tramadol, and increased risk of serotonin syndrome.

Caution with concomitant use of tramadol and SSRIs is recommended in patients who are already at increased risk for seizures.

OTHER OPIOIDS: a)While there is potential for increased risk of serotonin syndrome-like symptoms with the concomitant use of SSRIs and opioids, it appears to be relatively rare. Little evidence exists to suggests a contraindication to concomitant use; however, it is recommended to monitor for serotonin syndrome if used in patients with altered mental status, autonomic dysfunction, or those experiencing neuromuscular adverse effects.

b) Encourage patients to exercise regularly (ideally 30-60 minutes of aerobic exercise at least 5 times weekly) if possible, maintain a fibre intake of 25-30 grams/day, and not ignore the urge to defecate. Supplementary use of laxatives such as PEG 3350 may be necessary if it has been more than 3 days since they have had a bowel movement, or if constipation has become a chronic condition. Attempt to use the lowest effective dose of each agent to minimize this adverse effect.

Serious Risk for Harm

ALL OPIOIDS: Paroxetine can cause sleepiness, dizziness and confusion. Opioid use can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Serious Risk for Harm

DEXTROMETHORPHAN: When high doses of dextromethorphan are combined with paroxetine, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

Paroxetine can slow down the removal of dextromethorphan from your body. This could give you more side effects or put you at risk of serotonin syndrome (described above).

FENTANYL: When combined with paroxetine, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

HYDROMORPHONE: When combined with paroxetine, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

LOPERAMIDE:Use of both paroxetine and very high doses of loperamide (more than 100 mg in one day) can cause abnormal heart rhythm. Mixing these two medications could make the chance of having a deadly abnormal heart beat more likely, so this cocktail should be avoided.

MEPERIDINE: When combined with paroxetine, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

METHADONE: a) Methadone can slow down the removal of paroxetine from your body. This would be like taking extra paroxetine, and could cause more side effects.

b) Methadone and paroxetine can both affect heart rhythm. When methadone is combined with paroxetine, it could lead to a severe abnormal heart rhythm that is very dangerous and can even cause death.

MORPHINE: When combined with paroxetine, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

OXYCODONE: When combined with paroxetine, oxycodone is less effective for pain, and you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'. Additionally, paroxetine can slow down the removal of oxycodone from the body. This would be like taking extra oxycodone, and could cause more side effects or overdose.

TRAMADOL: When combined with paroxetine, tramadol is less effective for pain, and you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

If you have epilepsy taking tramadol with paroxetine could make you have seizures more often.

Think First

CODEINE: Painkillers with codeine may not work as well as expected when you are taking paroxetine.

ALL OPIOIDS: Taking paroxetine can make you constipated. Opioids can make this worse. To help keep your bowels moving properly, try to exercise for 30 to 60 minutes 5 times a week, eat high fibre foods (for example, whole grains and fruits like bananas and kiwi fruit), and don’t “hold it in” when you need to use the washroom.

See your pharmacist, nurse or doctor for advice about laxatives if constipation becomes problematic for you (for example, pain with bowel movements or more than 3 days between bowel movements).

Amphetamines/ Stimulants

uppers, ecstasy, E, X, Molly, mesc, XTC, love drug, MDA, MDE, Eve, MDMA, adam, disco biscuit, bennies, black beauties, Dexedrine®, Adderall®, dexies, Ritalin®, speed, crystal, meth, ice, glass, crank, tweak, cat, qat, kat, khat, bath salts, Ivory Wave, Vanilla Sky, Cloud 9

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Interaction

ALL AMPHETAMINES: a) Concomitant use of amphetamine derivatives or methylphenidate with SSRIs may increase a patient's risk of serotonin syndrome.

b) SSRIs may have amphetamine-like effects if abused.

c) It is possible that the combination of amphetamines and paroxetine may lead to neurotoxicity.

d) A case report of a 68-year-old woman who was taking paroxetine and dextroamphetamine concurrently presented to the emergency room with encephalopathy, along with tachycardia, tachypnoea, diaphoresis, rigidity, hyperreflexia and clonus. Given the rapid onset of symptoms, a diagnosis of serotonin syndrome was made.

ECSTASY/MDMA: a) Subjective and physiological effects of ecstasy were reduced in subjects given a single 100 mg oral dose of ecstasy following 3 days of paroxetine 20 mg daily. Increases in ecstasy's peak serum levels and AUC (17% and 27%, respectively) were also observed.

b) Similar results were observed in another study. The peak plasma levels and AUC (16% and 22%, respectively) of ecstasy increased when subjects were pre-treated with paroxetine. However, a decrease was seen in the peak plasma levels and AUC of 3-methoxy-4-hydroxymethamphetamine, a metabolite of ecstasy.

c) A patient experienced no ecstasy-associated effects upon initiating paroxetine 20 mg daily.

d) The combination of paroxetine and ecstasy may increase the risk of the syndrome of inappropriate antidiuretic hormone excretion (SIADH) and hyponatremia.

e) It is possible that the combination of ecstasy and paroxetine may lead to neurotoxicity.

Mechanism

ALL AMPHETAMINES: a) Additive effects of serotonin reuptake inhibition by psychostimulants (amphetamine derivatives or methylphenidate) and SSRIs could contribute to an increased risk of serotonin syndrome.

ECSTASY/MDMA: a,b) The exact mechanism of the interaction is unclear. Pharmacokinetic interactions may be due in part to CYP2D6 inhibition by paroxetine. The complex interaction may also be due to ecstasy's effects on serotonin in the brain.

d) The effects may be additive.

e) One possible effect of ecstasy is serotonin reuptake inhibition. The increased serotonergic effects could result in neurotoxicity.

Significance

ALL AMPHETAMINES: a) Additive effects of serotonin reuptake inhibition by psychostimulants (amphetamine derivatives or methylphenidate) and SSRIs could contribute to an increased risk of serotonin syndrome.

Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc) if psychostimulants are used concurrently with SSRIs.

ECSTASY/MDMA: a,c) Patients may not experience the same ecstasy 'high' when taking paroxetine; this may lead patients to take larger doses of ecstasy which could expose them to potentially life-threatening adverse effects.

d,e) Paroxetine should be avoided in patients who are known to take ecstasy due to this risk.

Serious Risk for Harm

When "street doses" of amphetamines or other stimulants are taken with paroxetine, it can cause: very high fever, sickness, dangerously high blood pressure, heart problems and even death. This is 'serotonin syndrome'.

Some medical reports show that taking paroxetine may make the amphetamine or ecstasy high milder than expected. This does not make it safe to take more stimulant.

Think First

Doctors will sometimes prescribe small amounts of medical amphetamines to patients taking paroxetine, to help treat certain illnesses, but this is done very carefully. Taking amphetamines without your doctor knowing is a risk.

Ketamine/ Phencyclidine

PCP, angel dust, PeaCe Pill, rocket fuel, love boat, embalming fluid, elephant tranquilizer, hog, illy, wet, wet stick, dipper, toe tag, cadillac, snorts, or surfer, Special K, vitamin K, CVR, cat tranquilizer, cat valium, jet, kit kat, Ketalar®

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Interaction

KETAMINE: a) As a CNS depressant, paroxetine has the potential to enhance the adverse or toxic effects of other CNS depressants, such as ketamine.

b) Concomitant administration of paroxetine and ketamine may result in decreased clearance of ketamine and increased serum levels.

PHENCYCLIDINE: No information currently available.

Mechanism

KETAMINE: a) Additive CNS depression.

b)This interaction appears to be due to moderate inhibition of CYP2B6 by paroxetine. Ketamine is a CYP2B6 substrate.

Significance

KETAMINE: a) It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

b) Concomitant use of paroxetine with ketamine may enhance the adverse/toxic effects of ketamine. Patients should be monitored for adverse effects and counselled to avoid ketamine while taking paroxetine.

Serious Risk for Harm

KETAMINE: Paroxetine can cause sleepiness, dizziness and confusion. Ketamine can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Paroxetine also slows the removal of ketamine from your body. This is like taking more ketamine than you planned. This combination could cause dangerously slowed breathing, or even death.

Unknown Dangers

PHENCYCLIDINE: Unknown dangers.

LSD/ Hallucinogens

acid, blotter, cartoon acid, hit, purple haze, trip, white lightning, raggedy ann, sunshine, window-pane, microdot, boomers, buttons, mesc, peyote, salvia, morning glory seeds, flying saucers, licorice drops, pearly gates, magic mushrooms, shrooms

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Interaction

LSD: a) In one study, 28 out of 32 subjects (88%) who had taken an antidepressant with inhibitory effects on serotonin reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3 weeks had a subjective decrease or virtual elimination of their responses to LSD. These data are in contrast with a previous study that reported increased responses to LSD during chronic administration of tricyclic antidepressants or lithium.

b) 3 case reports discuss patients with a history of LSD abuse who experienced onset or worsening of LSD flashbacks when given related SSRIs (fluoxetine, paroxetine or sertraline).

c) A randomized, double-blind, crossover study in 23 healthy participants found that 6 weeks of paroxetine pretreatment did not alter the pleasant subjective effects of LSD (100 µg) but significantly reduced “bad drug effect,” anxiety, and nausea compared with placebo.

Psilocybin: A retrospective anonymous survey of 611 participants who self-identified as having used a moderate or high dose of psilocybin during treatment with antidepressants, found the probability of reporting weaker than expected psilocybin effects during treatment with SSRIs.The probability of weaker effects was 0.47 with a 95% CI [0.40, 0.54] compared with using the same dose without antidepressants or compared with use by individuals not taking antidepressants.

Mechanism

LSD: The mechanism is not well understood. Increased levels of serotonin may lead to increased stimulation of 5-HT2 and 5-HT1A receptors, changes in extracellular brain serotonin concentrations, and changes in brain catecholamine systems.

c) LSD is partially metabolized by CYP2D6. As a strong CYP2D6 inhibitor, paroxetine increased LSD peak plasma concentrations by ~1.4-fold and overall exposure by ~1.5-fold.

Psilocybin: The mechanism of decreased psilocybin effects is likely to be 5-HT2A receptor downregulation due to long term use of SSRI. Subjective effects of psilocybin are known to be correlated with 5HT2A receptor occupancy.

Significance

LSD: There is limited information on the potential interactions between LSD and paroxetine. The authors of the case studies recommended warning patients with a history of LSD use of the potential for flashbacks or hallucinations.

c) The clinical significance remains uncertain. Concomitant use may increased the effects from LSD.

Psilocybin: The significance is uncertain, but concomitant use may reduce the effect of psilocybin.

Serious Risk for Harm

LSD: Mixing paroxetine with LSD can cause a bad trip, flashbacks of previous trips (even if it has been a while since you took LSD), or hallucinations. And sometimes, people have very 'mild' trips on LSD when they are taking these types of medicines. This may make you think it is safe to take more LSD than normal, but that could make you overdose.

Think First

Psilocybin (magic mushrooms): When taken with paroxetine, the “trip” effects from psilocybin like visual or sensory changes, and mood-boosting effects on depression or anxiety may not feel as strong. This may make you think it is safe to take more psilocybin than normal, but this could result in an overdose.

Think First

Some doctors may use psilocybin (magic mushrooms) and other hallucinogens as a treatment or add-on treatment for depression and anxiety, but this is done very carefully.

Benzodiazepines

benzos, downers, tranquilizers, tranks, Ativan®, Halcion®, Klonopin®, Rivotril®, Restoril®, Serax®, Valium®, Xanax®, Rohypnol® (roofies, rope, the forget or date rape pill)

Learn more about this substance »

Interaction
ALL BENZODIAZEPINES: As a CNS depressant, paroxetine has the potential to enhance the adverse or toxic effects of other CNS depressants, such as benzodiazepines.

ALPRAZOLAM: No interactions were found in a randomized, placebo-controlled study of 22 healthy subjects given paroxetine (20 mg daily) and alprazolam (1 mg daily) for 15 days.

CLONAZEPAM: A 39-year-old woman, who had been receiving paroxetine for 4 weeks, experienced increased anxiety, agitation, mild abdominal cramps and diaphoresis upon receiving one dose of clonazepam. It was suggested that she experienced serotonin syndrome, but this diagnosis has been questioned. She was successfully treated with lorazepam.

DIAZEPAM: No significant increase in adverse effects nor pharmacokinetic changes were observed in a study of 12 healthy subjects given paroxetine 30 mg daily along with diazepam 5 mg three times daily.

ETIZOLAM: A patient experienced symptoms of serotonin syndrome within 6 days of initiating a therapy regimen of paroxetine 20 mg, etizolam 1 mg and brotizolam 250 mcg. Paroxetine was discontinued and symptoms resolved over 10 days (resolution usually occurs within 24 hours).

OXAZEPAM: In one study, co-administration of oxazepam and paroxetine did not result in increased impairment of psychomotor skills.

ZALEPLON: A double-blind study gave paroxetine 20 mg daily for 9 days and a single dose of zaleplon 20 mg. Psychomotor performance was unaffected by the combination.

ZOLPIDEM: A case report describes a 16 year old girl who took paroxetine 20 mg daily for 3 days, at which point she took a 10 mg dose of zolpidem in the evening. She developed hallucinations within one hour and was unable to recognize her family. The symptoms resolved spontaneously within 4 hours.

Mechanism
ALL BENZODIAZEPINES: Additive CNS depression.

Unlike some other SSRIs, paroxetine only has weak inhibitory effects on CYP enzymes that metabolize benzodiazepines. Benzodiazepines that are not metabolized via CYP enzymes (e.g. lorazepam, oxazepam, and temazepam) are likely not affected by SSRIs.

Significance
ALL BENZODIAZEPINES: It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

While the risk of clinically relevant interactions between benzodiazepines and paroxetine appears to be low compared to other SSRIs, patients should be advised that the potential for interactions still exists and they should be monitored for any increases in adverse or toxic effects when starting, stopping or changing doses of either paroxetine or a benzodiazepine.

Serious Risk for Harm

Paroxetine can cause sleepiness, dizziness and confusion. Benzodiazepines can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Think First

Benzodiazepines are 'downers'. If you are depressed, blue, or moody, benzodiazepines can make this worse.

References

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also see FLUOXETINE

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Brookwell L, Hogan C, Healy D, et al. Ninety-three cases of alcohol dependence following SSRI treatment. Int J Risk Saf Med 2014; 26: 99-107.

Calvo G, Garcia-Gea C, Luque A et al. Lack of pharmacologic interaction between paroxetine and alprazolam at steady state in healthy volunteers. J Clin Psychopharmacol 2004; 24: 268-76.

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Cooper SM, Jackson D, Loudon JM et al. The psychomotor effects of paroxetine alone and in combination with haloperidol, amylobarbitone, oxazepam, or alcohol. Acta Psychiatr Scand Suppl 1989; 350: 53-5.

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