Repetitive Transcranial Magnetic Stimulation in Cancer Patients With Depression and Anxiety

Cancer is a leading cause of mortality and morbidity worldwide. In addition, cancer is associated with high rates of depression and anxiety among its sufferers, and cancer patients with depression usually have worse treatment outcomes and long-term survival. Surprisingly, many cancer patients with depression do not receive treatment for their depression, perhaps because treatments for cancer-related depression are usually adapted from those used in non-cancer populations and may not be suitable for cancer patients. Moreover, cancer patients with depression are more likely to have a long latency of anti-depressant drug action, negative drug-drug interactions with cancer chemotherapies and an increased susceptibility for systemic side effects. Repetitive transcranial magnetic stimulation (rTMS) is a new treatment modality for depression that affects the brain directly with no systemic side effects and poses no potential for drug-drug interactions. rTMS therapy was recently cleared by the FDA as an antidepressant treatment for treatment-resistant Major Depressive Disorder, and now is being evaluated for a wide array of additional psychiatric indications. This randomized, open label, two-arm, pilot study will investigate the safety, tolerability, feasibility and the efficacy of two forms of rTMS (i.e., left (fast) and right (slow) sided rTMS) in cancer-related depression. The study hypotheses are that rTMS will significantly reduce symptoms of depression and that right-sided slow rTMS will be more effective than left-sided fast rTMS for the treatment of severe anxiety.

Sex

All

Minimum age

22 Years

Maximum age

80 Years

Inclusion Criteria:

1\. Adults aged 22-80; 2. Have a previous diagnosis of cancer (any type or stage) as confirmed by official medical records; 3. Have a Diagnostic and Statistical Manual (DSM-IV) diagnosis of Major Depressive Disorder; 4. Have a Hamilton Depression Rating (HAM-D) 24-item score of more than 20; 5. Failed to receive satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current depressive episode; 6. All participants must have given signed, informed consent prior to registration in study.

Exclusion Criteria:

1\. Participant with any type of brain tumor; 2. Participant with cancer with brain metastases; 3. Evidence of the disease at the time of entry into the trial; 4. Presence or recent history of other concurrent cancers, with the following exceptions: a. Participants with completely treated basal or squamous skin cancers could be included in the study if their physicians deem that they are medically stable, b. Participants with completely treated in situ carcinoma of the breast or cervix could be included in the study if they have not had chemotherapy within the past month and their physicians deem that they are medically stable, c. Participants with pre-cancerous lesions in the colon could be included in the study if they have not had chemotherapy within the past month and their physicians deem that they are medically stable; 5. Participant had recent surgery within two weeks of screening; 6. Participants undergoing chemotherapy; 7. Participant pregnant or nursing; 8. Participant with any metallic object in or around their head; 9. Participant with a pacemaker; 10. Participants with unstable suicidal ideation as determined by the patient's treating psychiatrist; 11. Participants with a substance use disorder within the prior six months; 12. Significant history of head injury/trauma as defined by loss of consciousness for more than one hour; 13. Recurring seizures resulting from the head injury; 14. Clear cognitive sequelae from the head injury and cognitive rehabilitation following the injury; 15. Any disorder that would predispose the participant to seizures; 16. Use of concomitant medications that substantially increase seizure risk.; Such drugs could include neuroleptics (ex. haloperidol, droperidol), clozapine, tricyclic antidepressants (ex. amoxapine, clomipramine), bupropion (particularly the immediate release (IR) formulation), donepezil, psychostimulants (ex. methylphenidate), theophylline and/or other drugs that reduce the seizure threshold. For individuals on any of these medicines, a study clinician evaluated the drugs and doses to determine the risks and benefits. These were then discussed with the individual's Primary Care Physician to determine if the individual could be included in the study.

• BACKGROUNDBurgess C, Cornelius V, Love S, Graham J, Richards M, Ramirez A. Depression and anxiety in women with early breast cancer: five year observational cohort study. BMJ. 2005 Mar 26;330(7493):702. doi: 10.1136/bmj.38343.670868.D3. Epub 2005 Feb 4. PMID 15695497
• BACKGROUNDGeorge MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46. PMID 20439832
• BACKGROUNDJanicak PG, O'Reardon JP, Sampson SM, Husain MM, Lisanby SH, Rado JT, Heart KL, Demitrack MA. Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry. 2008 Feb;69(2):222-32. doi: 10.4088/jcp.v69n0208. PMID 18232722
• BACKGROUNDMachado S, Paes F, Velasques B, Teixeira S, Piedade R, Ribeiro P, Nardi AE, Arias-Carrion O. Is rTMS an effective therapeutic strategy that can be used to treat anxiety disorders? Neuropharmacology. 2012 Jan;62(1):125-34. doi: 10.1016/j.neuropharm.2011.07.024. Epub 2011 Jul 27. PMID 21807002
• BACKGROUNDO'Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, McDonald WM, Avery D, Fitzgerald PB, Loo C, Demitrack MA, George MS, Sackeim HA. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007 Dec 1;62(11):1208-16. doi: 10.1016/j.biopsych.2007.01.018. Epub 2007 Jun 14. PMID 17573044
• BACKGROUNDPaes F, Machado S, Arias-Carrion O, Velasques B, Teixeira S, Budde H, Cagy M, Piedade R, Ribeiro P, Huston JP, Sack AT, Nardi AE. The value of repetitive transcranial magnetic stimulation (rTMS) for the treatment of anxiety disorders: an integrative review. CNS Neurol Disord Drug Targets. 2011 Aug;10(5):610-20. doi: 10.2174/187152711796234943.