Method for augmenting the effects of serotonin reuptake inhibitors

Abstract

A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprises administering the subject a serotonin enhancer (e.g., a serotonin reuptake inhibitor) in an amount effective to treat the disorder; and concurrently administering the subject 5-hydroxytryptophan in an amount effective to enhance the activity of the serotonin enhancer, (e.g., serotonin reuptake inhibitor). In preferred embodiments the disorder is depression, anxiety, or substance abuse.

1 . A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprising:
 determining the presence or absence of a tryptophan hydroxylase 2 (Tph2) mutation in said subject; and then, if said subject possesses said Tph2 mutation;   administering said subject a serotonin reuptake inhibitor in an amount effective to treat said disorder; and   concurrently administering said subject 5-hydroxytryptophan in an amount effective to enhance the activity of said serotonin reuptake inhibitor;   to treat said serotonergic neurotransmission deregulation disorder.   
     
     
         2 . The method of  claim 1 , wherein said subject is a human subject. 
     
     
         3 . The method of  claim 2 , wherein said Tph2 is human Tph2 and said mutation encodes a change in an amino acid of the encoded protein, said amino acid selected from the group consisting of A65, V66, F68, L77, F84, I94, R97, E105, P152, W153, P155, D162, L175, R191, E211, V223, P244, G251, R276, P277, V278, R285, R294, P308, Y310, E313, A333, 1339, A342, S343, L344, A346, K353, V421, E423, A428, A436, R441, Y446, P449, Y450, and Q468. 
     
     
         4 . The method of  claim 2 , wherein said Tph2 mutation is selected from the group consisting of the human P449R mutation, the human R441H mutation, the human WI 53R mutation, the human A65V mutation, the human V66I mutation, the human L175V mutation, and the human Q468X (where X is a stop codon) mutation. 
     
     
         5 . The method of  claim 1 , wherein said serotonin reuptake inhibitor is selected from the group consisting of citalopram, fluvoxamine, fluoxetine, sertraline, paroxetine, escitalopram, duloxetine, venlafaxine, and pharmaceutically acceptable salts thereof. 
     
     
         6 . The method of  claim 1 , wherein said disorder is depression. 
     
     
         7 . The method of  claim 1 , wherein said disorder is anxiety. 
     
     
         8 . The method of  claim 1 , wherein said disorder is substance abuse. 
     
     
         9 . The method of  claim 1 , further comprising the step of concurrently administering said subject a peripheral decarboxylase inhibitor in an amount effective to reduce peripheral degradation of said 5-hydroxytryptophan. 
     
     
         10 . The method of  claim 9 , wherein said decarboxylase inhibitor is selected from the group consisting of carbidopa and benserazide. 
     
     
         11 .- 73 . (canceled) 
     
     
         74 . The method of  claim 1 , further comprising the step of concurrently administering said subject tetrahydrobiopterin. 
     
     
         75 . The method of  claim 1 , wherein said disorder is attention-deficit/hyperactivity disorder (ADHD). 
     
     
         76 . The method of  claim 1 , wherein said disorder is obsessive compulsive disorder. 
     
     
         77 . The method of  claim 1 , wherein said disorder is bipolar disorder.