Cross-over Study on the Influence of Fampridine on Working Memory in Mild Depression

Cognitive deficits, including working memory deficits, are often present in depression and there are currently no effective pharmacological treatments targeting working memory deficits. Papassotiropoulos et al. (2024) has recently demonstrated that fampridine, a potassium channel blocker, can enhance working memory in healthy individuals with lower baseline performance, suggesting it may hold potential for addressing cognitive deficits in clinical populations. The primary aim of this study is to evaluate whether fampridine improves working memory performance in mild depression

Randomized placebo-controlled phase II cross-over study on the influence of fampridine on working memory in mild depression The primary objective of this study is to evaluate if fampridine improves working memory in mild depression. It will also be assessed whether baseline working memory performance or subjective working memory deficits moderate the drug's effect.

The secondary objectives are to assess the influence of fampridine on different working memory functions, attention, cognitive flexibility, and mood.

Intervention:Twice daily oral administration of 10 mg fampridine (Fampyra®) for 7.5 days with a wash-out period of at least 6.5 days Control intervention:Twice daily oral administration of placebo for 7.5 days Study population:Total of 38 participants.

Eligibility Criteria:
Inclusion Criteria:

* Male or female
* Major depressive episode confirmed by the Mini-International Neuropsychiatric Interview. Currently mild (MADRS: 7-19).
* Normotensive (BP: 90/60mmHg - 140/90mmHg). Sufficiently treated hypertensive subjects will be included.
* BMI: 19 - 34,9 kg/m2
* Age: 18 - 30 years
* Fluent in German
* IC as documented by signature

Exclusion Criteria:

* Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to 4-aminopyridine
* Use of potassium channel blockers within the last 3 months
* Treatment with OCT 2 inhibitors and -substrates (e.g. cimetidine, propranolol)
* Treatment with antidepressants or antipsychotics within the last 3 months and throughout the study period
* Current intake of psychoactive drugs (e.g. benzodiazepines, antidepressants, neuroleptics).
* Other acute or chronic psychiatric disorder (e.g. psychosis, somatoform disorder, alcohol or drug abuse disorder)
* MADRS item 10 \> 0 (suicidal tendency)
* Risk of lowered seizure threshold (due to e.g. sleep deprivation, withdrawal of alcohol after alcohol abuse, hyponatraemia)
* History of seizures
* Acute cerebrovascular condition
* Acute renal failure or severe renal insufficiency (creatinine clearance \< 30 ml/min per 1.73 m2)
* Bradycardia \< 50/min during clinical examination.
* History of malignant cancers
* Walking problems (e.g. due to dizziness)
* Other clinically significant concomitant disease states (e.g. hepatic dysfunction, cardiovascular disease, diabetes, asthma)
* Clinically significant laboratory or ECG abnormality that could be a safety issue in the study
* Severe somatic or neurological comorbidities
* Smoking (\>5 cigarettes per day)
* Pregnancy or breast feeding. Intention to become pregnant during the study participation.
* Known or suspected non-compliance
* Inability to follow the procedures of the study, e.g. due to language or psychological problems of the participant
* Participation in another study with an investigational drug within the 30 days preceding and during the present study
* Prior participation (less than two years ago) in a study investigating working memory (notably the n-back task)
* Enrolment of the investigator, his/her family members, employees and other dependent persons