Αντικαταθλιπτικό ή αντιψυχωσικό;
Εχει αποδειχτεί ότι κάποια από τα νευρομεταβιβαστικά κυκλώματα όπως το γλουταμινικό και το ντοπαμιναργικό που αρχικά είχαν συσχετιστεί με την ψύχωση και τις γνωστικές διαταραχές, παίζουν επίσης ρόλο και στη ρύθμιση του συναισθήματος.
- Το αντικαταθλιπτικό bupropion (Wellbutrin) αναστέλει την επαναπρόσληψη (δηλαδή αυξάνει την διαθεσιμότητα) της νοραδρεναλίνης αλλά και της ντοπαμίνης.
- Διάφορες πρωτεΐνες αλληλεπιδρούν με τους D2 υποδοχείς της ντοπαμίνης και ρυθμίζουν την καταθλιπτική συμπεριφορά σε πειράματα σε ζώα1,2.
- Ο άμεση αντικαταθλιπτική δράση του γλουταμινικού οξέος (glutamate) έχει αποδειχθεί ήδη3.
Αφού λοιπόν τα αντικαταθλιπτικά και τα αντιψυχωσικά δεν είναι παρά συμπτωματικές θεραπείες (δηλαδή απευθύνονται στο σύμπτωμα και όχι στην αιτία της νόσου), γίνεται φανερό ότι δεν έχει και τόσο μεγάλη σημασία η διάγνωση με την οποία χαρακτηρίζουμε τον ασθενή. Σημασία έχει κυρίως να εστιάσουμε στο σύμπτωμα και να επιλέξουμε την απλούστερη και παράλληλα την πιό αποτελεσματική θεραπεία με τις λιγότερες παρενέργειες. Μία από τις βασικές αρχές βέβαια της θεραπείας εξακολουθεί να είναι η χρήση όσο το δυνατόν λιγότερων φαρμάκων στους διάφορους συνδυασμούς. Με τον τρόπο αυτό περιορίζονται και οι πιθανότητες απρόβλεπτων παρενεργειών.
Θεραπευτικές στρατηγικές
Για την αντιμετώπιση περιπτώσεων όπου έχουμε ταυτόχρονη συνύπαρξη καταθλιπτικών και ψυχωτικών συμπτωμάτων, μπορούν βεβαίως να χρησιμοποιηθούν μαζί αντικαταθλιπτικά και αντιψυχωτικά φάρμακα. Μπορεί επίσης να χρησιμοποιηθούν και φάρμακα που είναι αποτελεσματικά και στις δύο αυτές κατηγορίες των συμπτωμάτων. Αρκετά φάρμακα που αρχικά είχαν εγκριθεία από το FDA (Διεύθυνση Τροφίμων και Φαρμάκων των ΗΠΑ) ώς αντιψυχωτικά πήραν αργότερα έγκριση για θεραπεία ενίσχυσης (augmentation therapy) σε δύσκολα περιστατικά κατάθλιψης. Η τάση αυτή άρχισε με την Κουετιαπίνη (Seroquel) για να συνεχιστεί με την Αριπιπραζόλη (Abilify) και με ένα σύνθετο σκεύασμα που αποτελείται από Ολανζαπίνη και Φλουοξετίνη (Zyprexa+Ladose, δεν κυκλοφορεί στην Ελλάδα).
Βασικό μέλημα του γιατρού στους συνδυασμούς φαρμάκων είναι να περιορίσει τις παρενέργειες που μπορεί να εμφανίσει το κάθε φάρμακο, οι οποίες συχνά πολλαπλασιάζονται όταν χορηγούνται συνδυασμοί. Τα περισσότερα αντικαταθλιπτικά αυξάνουν τη διαθεσιμότητα μονοαμινών στον εγκέφαλο όπως την νοραδρεναλίνη, τη σεροτονίνη ή τη ντοπαμίνη. Αντιστρόφως, ολα τα αντιψυχωτικά συνδέονται σε μικρό ή μεγαλύτερο βαθμό με τους D2 ντοπαμινεργικούς υποδοχείς. Οι συνδυασμοί που μπορούν να προκύψουν είναι αμέτρητοι με αποτέλεσμα να έχουμε άλλοτε ορθοστατική υπόταση, καταστολή, σεξουαλική δυσλειτουργία και ανορεξία και άλλοτε δυσκοιλιότητα, ξηροστομία, ταχυκαρδία ή σύγχυση.
1. Haque FN, Lipina TV, Roder JC, Wong AH. Social defeat interacts with Disc1 mutations in the mouse to affect behavior. Behav Brain Res. 2012;233:337-344.
2. Pei L, Li S, Wang M, et al. Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects. Nat Med. 2010;16:1393-1395.
3. Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481-486.
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