sertraline

AKA

Zoloft®, AG-Sertraline®, Apo-Sertraline®, Auro-Sertraline®, Bio-Sertraline®, Mar-Sertraline®, Mint-Sertraline®, NRA-Sertraline®, PMS-Sertraline®, Priva-Sertraline®, Riva-Sertraline®, Teva-Sertraline®, Van-Sertraline® 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) In a study where subjects were given sertraline in doses up to 200 mg for 9 days, sertraline did not appear to impair cognitive or psychomotor performance or seem to potentiate the effects of alcohol.

b) 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.

c) 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 patient, re-exposure to the same or a related antidepressant reproduced this finding. 32 of these patients reported an increased or altered pattern of alcohol use after SSRI initiation.

Mechanism
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) According to the information currently available, sertraline does not appear to interact with alcohol.

b) Patients started on sertraline should be monitored for increased alcohol cravings or consumptions.

c) It is possible that patients initiating SSRI therapy may experience higher levels of intoxication with amounts of alcohol that they previously tolerated. Patients 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 sertraline 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 sertraline with alcohol doesn't seem to change the risk of drinking alcohol in moderation. This means your usual dose of sertraline 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 sertraline 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 showed significantly lower concentration-to-dose ratios of sertraline and its metabolite (desmethylsertraline) than non-smokers. In contrast, another study showed no correlation between sertraline serum levels and smoking status.

Mechanism
In the study that did find an interaction, the patients were also taking other medications that may have accounted for these interactions.

Significance
It is unclear whether smoking has an effect on the pharmacokinetics of sertraline.

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
No information currently available.

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 sertraline to help with anxiety, this may work against the helpful effects of sertraline.

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, sertraline has the potential to enhance the adverse or toxic effects of other CNS depressants such as cannabis.

b) Cannabis may theoretically result in reduced sertraline metabolism.

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

b) Cannabidiol (CBD) inhibits CYP3A4, although this has not yet been proven at doses used in human studies. Sertraline is a partial CYP3A4 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 sertraline and using cannabis may experience increased adverse effects from sertraline.

Serious Risk for Harm

Sertraline 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, especially in high doses, can cause anxiety. If you are taking sertraline for anxiety, cannabis could work against the helpful effects of sertraline.

Think First

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

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 sertraline leading to increased serum levels. 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 sertraline; however, to what extent cocaine inhibits the metabolism of sertraline is unclear.

b) Taking sertraline may result in decreased clearance of cocaine and increased serum levels.

c) Two studies investigated the addition of related medication escitalopram to modafinil with the goal of attenuating the euphoric effects of cocaine. The combination did not reduce cocaine's effects or working memory in cocaine users more than modafinil alone.

d) On day 1-5, compared to placebo, related medication escitalopram resulted in a significant decrease in attentional bias to cocaine-related words. This effect was not found after day 5.

e) Concomitant use of cocaine and sertraline may theoretically lead to development of serotonin syndrome.

f) Concomitant use of sertraline 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 sertraline, a CYP2D6 substrate.

b) Sertraline is a weak CYP3A4 inhibitor and can inhibit metabolism of cocaine, a CYP3A4 substrate.

c) It is hypothesized that this may be due to activation of 5-HT2C receptors due to the increased levels of 5-HT when escitalopram is administered.

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

f) Additive QTc prolongation.

Significance
a,b) Concomitant use of cocaine and sertraline may enhance the adverse/toxic effects of either drug. Patients should be monitored for the appearance of adverse drug effects and counseled to avoid use of cocaine while taking sertraline.

c) Escitalopram does not appear to reduce the effects of cocaine. It is unknown if this also applies to sertraline.

d) No long-term effects of escitalopram on attentional-bias to cocaine related words was found. This indicates that SSRIs would not be effective as treatment for cocaine dependence.

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

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

Serious Risk for Harm

If you are taking sertraline, 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

Cocaine and sertraline can both affect heart rhythm. When cocaine is combined with sertraline, it could lead to a severe abnormal heart rhythm that is very dangerous and can even cause death.

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, sertraline has the potential to enhance the adverse or toxic effects of other CNS depressants such as opioids.

DEXTROMETHORPHAN: a) One case study reports that a 6-year-old patient developed serotonin syndrome after ingesting dextromethorphan overdoses while receiving sertraline.

b) One case study reports a 20-year-old man who developed serotonin syndrome after ingesting dextromethorphan overdoses, while receiving a related drug, escitalopram.

c) Healthy subjects were given sertraline 100 mg daily for 8 days and then a single 30 mg dose of dextromethorphan. There did not appear to be any change in the ratio of dextromethorphan to dextrorphan (metabolite).

d) 12 healthy volunteers were given sertraline 50 mg daily for 3 days, then 100 mg daily for 10 days, and a dose of dextromethorphan 30 mg on days 5 and 10. The mean CYP2D6 inhibition half life was 3 days; the inhibitory effects persisted 5 days after sertraline was discontinued. The ratio of dextromethorphan to dextrorphan increased 15.6-fold, although there was wide inter-patient variability.

FENTANYL: A case report describes a case of serotonin syndrome in a 46 year old woman taking sertraline 50 mg daily and cetirizine 10 mg daily after receiving fentanyl 50 micrograms and midazolam and propofol for surgery.

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 sertraline. 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) A placebo-controlled study involving 31 depressed patients taking methadone found that sertraline increased the concentration-to-dose ratio of methadone by 26%, and the placebo group had a 16% decrease in the ratio at 6 weeks. At 12 weeks the ratios shifted toward baseline.

b) Concomitant administration of methadone with sertraline may result in decreased clearance of sertraline and increased serum levels. The potential for CYP2D6 inhibition puts patients taking these two drugs at increased risk of adverse or toxic effects associated with higher levels of sertraline; however, to what extent the metabolism of sertraline is inhibited is unclear.

c) A 31-year-old woman receiving methadone 230 mg daily developed asymptomatic prolonged QTc interval upon the initiation of sertraline 50 mg daily. Her QTc interval normalized upon the withdrawal of both medications.

d) In a placebo-controlled study, researchers observed a 26% increase in methadone's plasma/dose ratio in 31 depressed, methadone-maintained patients after 6 weeks of concomitant use of methadone and sertraline. A 16% decrease was observed in the placebo group; however, after 12 weeks of therapy, the ratios trended towards baseline values. Both groups experienced similar adverse effects.

OXYCODONE: a) Symptoms of serotonin syndrome (severe tremors, visual hallucinations) developed in a patient who had received a bone-marrow transplant patient and was taking sertraline 50 mg daily, cyclosporine 75 mg daily, and oxycodone (200 mg over a 48-hour period). Initially, cyclosporine-induced adverse effects were suspected and both cyclosporine and oxycodone were temporarily discontinued. His hallucinations, but not tremors, lessened. It was only when sertraline was discontinued and cyproheptadine (a serotonin antagonist) started that his tremors resolved.

b) A case report describes possible serotonin syndrome in an elderly patient taking sertraline and extended-release oxycodone.

TRAMADOL: a) Sertraline reduces the therapeutic effects of tramadol due to reduced formation of the active metabolite responsible for opioid-like effects. However, some analgesic effect remains due to serotonin and norepinephrine reuptake inhibition.

b) A 42-year-old woman who had been taking sertraline for the previous year developed symptoms of serotonin syndrome (sinus tachycardia, confusion, psychosis, sundowning, agitation, diaphoresis, tremor) 3 weeks after starting tramadol (150 mg increased to 300 mg daily in 50 mg increments every 2 to 3 days).

c) A second case report describes an 88-year-old woman taking sertraline 50 to 100 mg daily who developed altered cognitive function, tremor, ataxia, and muscle weakness 10 days after starting tramadol. As serotonin syndrome was suspected, sertraline was discontinued over a 2 day period and the tramadol dose was halved. The patient's symptoms resolved over the next 2 weeks.

d) A 55 year old man taking sertraline and suspected of abusing tramadol developed serotonin syndrome.

e)A 75 year old woman taking tramadol 50 mg daily for 3 days initiated sertraline 50 mg/day and experienced serotonin syndrome. The concentration of serotonin in her cerebrospinal fluid was found to be 38.5 ng/mL (normal is less than 10 pg/mL).

f) An increase in seizure risk was noted by the manufacturer of tramadol when used with SSRIs.

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

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

DEXTROMETHORPHAN: a,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.

c,d) Sertraline inhibits CYP2D6 which metabolizes dextromethorphan.

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

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

METHADONE: a) Sertraline inhibits CYP2D6 and CYP3A4 leading to decreased metabolism of methadone.

b) Both methadone and sertraline are moderate CYP2D6 inhibitors.

c) Sertraline and methadone are both QTc prolonging agents.

TRAMADOL: a) Sertraline inhibits CYP2D6 which converts tramadol to its active metabolite.

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

OTHER OPIOIDS: Additive serotonergic effects.

Significance
ALL OPIOIDS: b) 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.

DEXTROMETHORPHAN: a,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.

c,d) There is conflicting evidence about whether the CYP2D6 inhibition is significant enough to increase dextromethorphan levels.

FENTANYL, METHADONE, MEPERIDINE, TRAMADOL: These may not be the best choice for analgesic therapy in patients currently maintained on sertraline due to the potential for sertraline to increase the risk of serotonin syndrome.

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

METHADONE: Concomitant use of methadone and sertraline may enhance the adverse/toxic effects of the either drug. Patients should be monitored for the appearance of adverse drug effects and counselled to avoid methadone while taking sertraline.

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

TRAMADOL: Tramadol may be less effective in patients taking sertraline.

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

OTHER OPIOIDS: 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.

Serious Risk for Harm

ALL OPIOIDS: Sertraline 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

LOPERAMIDE:Use of both sertraline 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.

METHADONE: Sertraline can slow down the removal of methadone from the body. This would be like taking extra methadone, and could cause more side effects or even an overdose. Methadone can also slow down the removal of sertraline from the body, and give you more side effects from sertraline.

Serious Risk for Harm

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

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

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

TRAMADOL: When combined with sertraline, 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 sertraline could make you have seizures more often.

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 psychostimulants (amphetamine derivatives or methylphenidate) and 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 sertraline may lead to neurotoxicity.

ECSTASY/MDMA: a) SSRIs may block the psychoactive effects of ecstasy. This is based on data and case reports from other SSRIs.

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

c) It is possible that the combination of ecstasy and sertraline may lead to neurotoxicity.

METHYLPHENIDATE: a) There is a case report of a 12-year-old girl experiencing generalized seizures while receiving methylphenidate for treatment of ADHD and oppositional defiant disorder plus sertraline for a co-morbid anxiety disorder.

b) A 13-year-old boy experienced a tonic-clonic seizure after 2 weeks of concomitant use of sertraline 25 to 50 mg daily and long-acting methylphenidate 80 mg daily. Prior to the introduction of sertraline, he had experienced no significant adverse affects associated with methylphenidate monotherapy. There was no recurrence of seizures after the discontinuation of sertraline.

c) There is a case report of a 62-year-old woman who developed serotonin syndrome during treatment with methylphenidate and sertraline.

d) A 14-year-old boy with Prader-Willi syndrome (PWS) taking methylphenidate for ADHD was started on sertraline 50 mg twice daily for temper tantrums, uncontrollable eating and skin-picking. Methylphenidate was discontinued a year later when the severity of skin-picking increased and the symptom of self-talking emerged. The symptoms subsided and he continued to receive sertraline for the following 6 months until he developed delusions. His psychotic symptoms improved with the commencement of risperidone.

e) A 15-year-old with PWS and a family history of bipolar illness was diagnosed with ADHD and started on methylphenidate 18 mg daily. Five weeks later, sertraline 50 mg daily was added to help control his temper tantrums and compulsive repetitive speech. After a month of concomitant therapy, he experienced a reduced need for sleep, became hypertalkative, and irritable. Medication-induced mood disorder was suspected and he was admitted to hospital for treatment. Sertraline was discontinued and he experienced no further manic episodes.

f) Sertraline therapy was augmented with methylphenidate in a 61-year-old diagnosed with major depression. His symptoms improved and his dose of methylphenidate was increased to 5 mg twice daily from 2.5 mg twice daily. The patient developed visual hallucination and confusion several days after the dose increase. His psychosis resolved following the discontinuation of methylphenidate.

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.

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

ECSTASY: a) These findings suggest that physiological and psychological effects of MDMA in humans are partially due to an interaction of MDMA with the serotonin transporter and a subsequent release of serotonin. This could theoretically be blocked by SSRIs.

b) The effects may be additive.

METHYLPHENIDATE: a,b) Methylphenidate and sertraline can both lower the seizure threshold.

Significance
ALL AMPHETAMINES: 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: a) The effects of ecstasy may be decreased while taking sertraline.

b) Sertraline should be avoided in patients who are known to take ecstasy due to this risk.

METHYLPHENIDATE: a,b) It is possible that methylphenidate and sertraline increase the risk of seizures, although it is unclear if this was the cause in the case report described. This medication combination is prescribed relatively commonly. There is limited data on the relative effects of antidepressants and stimulant medications on seizure threshold.

Serious Risk for Harm

When "street doses" of amphetamines or other stimulants are taken with medicines in the same family as sertraline, 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 sertraline 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 sertraline, to help treat certain illnesses, but this is done very carefully. Taking amphetamines without your doctor knowing is a risk.

Phencyclidine/ Ketamine

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, sertraline has the potential to enhance the adverse or toxic effects of other CNS depressants, such as ketamine.

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

PHENCYCLIDINE: Concomitant administration of sertraline and phencyclidine may result in decreased clearance of phencyclidine and increased serum levels.

Mechanism
KETAMINE: b) Additive CNS depression.

a) This interaction appears to be due to moderate inhibition of both CYP2B6 and CYP3A4 by sertraline. Ketamine is a CYP2B6 and CYP3A4 substrate.

PHENCYCLIDINE: Sertraline is a moderate CYP3A4 inhibitor, and phencyclidine is a CYP3A4 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 sertraline with ketamine may enhance the adverse/toxic effects of ketamine. Patients should be monitored for adverse effects and counselled to avoid ketamine while taking sertraline.

In patients taking sertraline and using ketamine, sudden changes in ketamine use, could result in either sub-therapeutic effects or increased risk of adverse/toxic effects of sertraline.

PHENCYCLIDINE: Concomitant use of sertraline with phencyclidine may enhance the adverse/toxic effects of phencyclidine. Patients should be monitored for adverse effects and counselled to avoid use of phencyclidine.

Serious Risk for Harm

KETAMINE: Sertraline slows the removal of ketamine from your body. This is like taking more ketamine than you planned. This cocktail could cause dangerously slowed breathing or even death.

Sertraline 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.

Serious Risk for Harm

PHENCYCLIDINE (PCP): Sertraline slows the removal of phencyclidine from your body. This is like taking more phencyclidine than you planned. This cocktail can cause seizures, dangerously high blood pressure or body temperature, and destruction of your muscles.

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
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 sertraline or related SSRIs fluoxetine or paroxetine.

Mechanism
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.

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

Serious Risk for Harm

Mixing medicines in the same family as sertraline with LSD can cause a bad trip, flashbacks of previous trips (even if it has been a while since you took LSD), or hallucinations.

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. Other people have said that taking these types of medicines gave them a stronger than usual response to LSD. It is hard to predict how you will react to the combination.

Benzodiazepines

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

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

ALPRAZOLAM: a) No significant pharmacokinetic changes were observed in 10 healthy subjects co-administered sertraline and a single dose of alprazolam. Sertraline did not appear to enhance the psychomotor effects of alprazolam either with the exception of a decrease in peak performance in the manual tracking test.

b) Similarly, a second study in 12 subjects found no pharmacokinetic interactions after 2 weeks of concomitant use of alprazolam and sertraline.

CLONAZEPAM: A placebo-controlled, randomized, double-blind, crossover study in 13 subjects, who were given sertraline 100 mg along with clonazepam 1 mg for 10 days, found no pharmacokinetic or pharmacodynamic interactions.

DIAZEPAM: A 13% reduction in diazepam clearance was observed when subjects were given a single intravenous dose of diazepam after 21 days of treatment with sertraline. Researchers suggested this was unlikely to be clinically relevant. The effect of sertraline on repeated doses of oral diazepam was not investigated.

ZOLPIDEM: a) One case report describes visual hallucinations lasting 7 hours that occurred in a patient taking benzodiazepine-related drug zolpidem and sertraline.

b) The pharmacokinetics of zolpidem do not appear to be significantly altered by sertraline.

Mechanism
ALL BENZODIAZEPINES: Additive CNS depression.

Sertraline has little inhibitory activity on the 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 sertraline 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 sertraline or a benzodiazepine.

Serious Risk for Harm

Sertraline 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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