Could tramadol make my schizophrenia worse?

Against common sense and better judgment

Pay attention to interactions with SSRIs

The SSRIs approved for obsessive-compulsive disorder mainly include older substances such as paroxetine and fluoxetine. In addition to the very long half-life of fluoxetine, it should be noted that these two drugs are among the very strong inhibitors of CYP2D6. About 25 percent of all drugs are metabolized via CYP2D6. Particularly with psychotropic drugs such as amitriptyline or risperidone, which patients receive for example because of accompanying depression or aggressiveness, and beta blockers such as metoprolol, caution is advised here. But substances such as tramadol or tamoxifen are also affected. Paroxetine or fluoxetine should not be taken concomitantly with CYP2D6 substrates.

Like clomipramine, all SSRIs can prolong the QT time and thus trigger life-threatening arrhythmias. This risk appears to be particularly high with simultaneous treatment with other substances that can prolong the QT time, for example ciprofloxacin or neuroleptics, especially if these can systemically inhibit CYP enzymes, for example clarithromycin. Other risk factors are bradycardia, hypocalemia and hypomagnesaemia, advanced age, and female gender.

Particularly relevant for older patients: SSRIs promote hyponatremia and increase the tendency to bleed. For platelets to aggregate naturally, it is important that they can release serotonin. Without a nucleus, platelets cannot synthesize serotonin, so they have to absorb it from the outside - and this mechanism is blocked by SSRIs. This can be particularly relevant in patients who are also taking other anticoagulants. It should be noted that the actual platelet aggregation cannot be determined in everyday clinical practice.

Both clomipramine and SSRIs must not be combined with other medicinal products that increase the concentration of the monoamine serotonin. The classics are the inhibitors of monoamine oxidase (MAO) and other SSRIs. Due to the different elimination half-lives of the substances, washout phases are recommended when changing therapy (Table 4). Fluoxetine plays a special role here because it has an extremely long half-life: five to six weeks after stopping it, there is still an active substance in the body.

Doctors and pharmacists should pay attention to whether the patient develops signs of serotonin syndrome. This manifests itself from increased sweating to agitation, nausea, diarrhea, vomiting, hyperthermia and hyperreflexia to seizures. Non-psychotropic drugs such as the cough suppressant dextromethorphan, the pain reliever tramadol and the antibiotic linezolid can also increase the serotonin concentration and should not be combined with (S) SRIs or MAO inhibitors.

SSRI: differences in detail

In addition to the pharmacokinetic differences and group effects of the SSRIs, there are indications for special advantages and disadvantages of the individual substances. Of all SSRIs, sertraline seems to be the least likely to lead to an increase in prolactin, which is beneficial in the treatment of patients in puberty, postmenopausal women or women with galactorrhea or unexplained amenorrhea. At the same time, the risk of gastrointestinal side effects such as diarrhea is higher with sertraline than with other SSRIs, which can be relevant in patients with inflammatory bowel disease or irritable bowel syndrome.

Sertraline and fluoxetine can cause more insomnia, whereas paroxetine and fluvoxamine are more drowsy. The latter may therefore be more suitable if the obsessive-compulsive disorder occurs together with an anxiety disorder. Citalopram and escitalopram are largely neutral in terms of sleep and are suitable for patients whose sleep rhythm has been impaired by other SSRIs. Since both active ingredients are not very sensitive to CYP interactions, they are suitable for patients taking several drugs.

Sexual dysfunction and weight gain are more common with paroxetine than with the other SSRIs. Fluoxetine, on the other hand, is most suitable for patients with accompanying eating disorders, as body weight rarely increases during therapy.