Lamotrigine Augmentation in Resistant Depression

Inclusion Criteria: 1. Male or female subjects, age 18-65 2. A current primary diagnosis of unipolar major depression based on certain criteria 3. Have a score of \> 18 on the 17-item Hamilton Depression scale 4. A history of prior failure of at least one adequate trial of an FDA-approved antidepressant. The antidepressant failure must have occurred within the current episode of major depression 5. Females of childbearing potential will be allowed as long as they are taking adequate contraceptive precautions Exclusion Criteria: 1. A primary Axis I diagnosis other than primary unipolar major depression 2. A history suggestive of hypomania or mania during the current episode or during the person's lifetime 3. A history of psychosis, dementia, organic affective disorders or alcohol and/or substance abuse in the previous six months * Individuals with a current or past diagnosis of schizoid, schizotypal, borderline or antisocial or any other current or past severe personality disorder * Individuals with a current or past diagnosis of schizophrenia or schizoaffective disorder 4. A history of failure to respond to electroconvulsive therapy during the current or any prior lifetime episode of major depression 5. A history of failure of a prior adequate trial of paroxetine or paroxetine-CR for the treatment of Major Depression 6. Significant, coexisting medical conditions that might make it unsafe to take either of the study medications, or in which any average reasonable clinician would assume that the medical condition may, in fact, be exacerbating the current episode of depression or impede the person's ability to recover fully from their depressive illness 7. Presence of significant medical abnormalities on baseline laboratory values or physical examination, including vital signs * Individuals with any significant abnormalities of thyroid function * Subjects on thyroid supplementation must have been on a stable dose for six months prior to the screening visit 8. Individuals who will require concomitant psychotropic medications, including benzodiazepines * Subjects with severe insomnia will be allowed to take a maximum of 10 mg of zolpidem on two nights weekly at the investigator's discretion. * Zolpidem may not be taken on the night before the study visit. * Each dose of zolpidem should be listed on the concurrent medication case report form 9. Medications likely to cause significant effects on mood and anxiety are also excluded 10. Individuals with a positive urine drug screen for drugs of abuse at the screening visit 11. Use during the time of the study of any medications known to affect the metabolism of lamotrigine * Individuals on valproate and carbamazepine will be specifically excluded * Investigators should be aware that oral contraceptives have been reported to lower the levels of lamotrigine, but any change in dosing is left to the judgment of the investigator 12. Subjects who have taken other psychoactive drugs within certain time frames of the screening visit 13. The presence of significant risk of suicide 14. Pregnant females or those who are breastfeeding infants 15. A history of hypersensitivity or intolerance to either of the study medications, lamotrigine or paroxetine or paroxetine-CR 16. Subjects initiating or terminating psychotherapy within 12 weeks of the screening visit 17. Individuals who are currently on disability for a psychiatric disorder, or who are in any other way likely to experience considerable secondary gain from the persistence of their psychiatric illness, such as pending legal litigation of any type 18. Individuals who in the opinion of the investigator would not be able to understand or comply with the study requirements