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.

That which is claimed is: 
     
         1 . A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, comprising:
 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;   wherein said subject is non-responsive or insufficiently responsive to treatment therapy with a serotonin reuptake inhibitor alone.   
     
     
         2 . The method of  claim 1 , wherein said subject has been predetermined to have at least one Tph2 mutation. 
     
     
         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, I339, 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 W153R 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 unipolar major depression. 
     
     
         9 . The method of  claim 1 , wherein said disorder is bipolar disorder. 
     
     
         10 . The method of  claim 1 , wherein said disorder is obesity. 
     
     
         11 . The method of  claim 1 , wherein said subject is a human subject. 
     
     
         12 . A method of treating a subject for a serotonergic neurotransmission dysregulation disorder, wherein said subject is being treated with a serotonin reuptake inhibitor, comprising:
 determining whether the subject is non-responsive or insufficiently responsive to treatment therapy with a serotonin reuptake inhibitor alone; and then, if said subject is non-responsive or insufficiently responsive to said serotonin reuptake inhibitor;   administering said subject 5-hydroxytryptophan in an amount effective to enhance the effects of said serotonin reuptake inhibitor to treat said disorder.   
     
     
         13 . The method of  claim 12 , wherein said subject has been predetermined to have at least one Tph2 mutation. 
     
     
         14 . The method of  claim 12 , wherein said serotonin reuptake inhibitor is a selective serotonin reuptake inhibitor. 
     
     
         15 . The method of  claim 12 , wherein said serotonin reuptake inhibitor is italopram, fluvoxamine, fluoxetine, sertraline, paroxetine, escitalopram, duloxetine, or venlafaxine, or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 12 , wherein said disorder is depression. 
     
     
         17 . The method of  claim 12 , wherein said disorder is anxiety. 
     
     
         18 . The method of  claim 12 , wherein said disorder is unipolar major depression. 
     
     
         19 . The method of  claim 12 , wherein said disorder is bipolar disorder. 
     
     
         20 . The method of  claim 12 , wherein said disorder is obesity. 
     
     
         21 . The method of  claim 12 , wherein said subject is a human subject.