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About one third of patients with major depression don't respond to first-line treatments; 15% are resistant to all treatments (treatment-resistant depression [TRD]). After successfully treating TRD in a patient deficient in cerebrospinal fluid (CSF) tetrahydrobiopterin (necessary for biosynthesis of several neurotransmitters) with sapropterin (synthetic form of tetrahydrobiopterin's active isomer), investigators searched for this and other potential metabolic abnormalities in 33 TRD patients.
Patients had failed >3 medication trials (mean age, 26; 76% women; age at onset: ≤17 years, 91%; <10 years, 33%); 85% had comorbid diagnoses, primarily anxiety disorders, post-traumatic stress disorder, or both. Of their first-degree relatives, 82% had …