The purpose of the study is to estimate the ability of mirtazapine to reduce depression, nausea, and vomiting, and maintain weight in depressed glioma patients undergoing Temozolomide (TMZ) therapy. Of equal importance, the investigators will monitor the tolerability of Mirtazapine in these patients over the course of the study.

Research Hypothesis: For glioma patients undergoing TMZ chemotherapy, Mirtazapine will address TMZ-associated nausea and vomiting (CINV) and weight loss in addition to depression. Mirtazapine acts as an antagonist at the 5-HT3 receptor, which may explain its anti-emetic properties. Mirtazapine is also an appetite stimulant, which may help curb the weight loss associated with TMZ chemotherapy.

Specific aim 1: To administer the Beck Depression Inventory to approximately 100 patients meeting the inclusion/exclusion criteria in order to identify at least 36 with clinical depression (defined as total score >= 21).

Specific aim 2: To put at least 36 clinically depressed patients identified in aim one on mirtazapine for eight weeks.

Specific aim 3: To administer the Beck Depression Inventory to patients from aim two at four weeks and at eight weeks of treatment with mirtazapine.

Specific aim 4: To document weight and frequencies of nausea, vomiting, and insomnia among participants over the course of the study.

Specific aim 5: To document adverse events experienced by participants over the course of the study and determine, to the extent possible, if mirtazapine is the cause.

The investigators will:

1. Assess changes in the distribution of depression scores as measured by the Beck Depression Inventory (a self-administered instrument extensively used and validated in glioma studies) from baseline to after eight weeks of treatment with mirtazapine.
2. Assess changes in nausea, vomiting, Sleeping and body weight between baseline and the eight-week follow-up visit,
3. Document the trajectory of changes in depression, nausea, vomiting, and weight over the three study time points (baseline, four-week, and eight-week visit).
4. Lastly, collect information on the tolerability of mirtazapine in our patient population.

Main Research Hypothesis: The investigators hypothesize that the mirtazapine regimen will improve depression scores at eight-weeks, compared to baseline scores. Further, the investigators hypothesize that the mirtazapine regimen will limit the reduction of weight and the incidence of nausea/vomiting and insomnia at eight weeks compared to baseline.

Inclusion Criteria:

• Understand and voluntarily sign and date an informed consent document prior to any study related assessments/procedures are conducted.
• Histologically confirmed diagnosis of glioma
• No prior treatment with temozolomide TMZ
• Patient will receive temozolomide TMZ therapy as part of their standard treatment.
• Males and Females ≥18 years of age at the time of signing the informed consent document. Able to understand consent forms and study materials in English
• Willing to use approved methods of contraception for duration of study
• Karnofsy Performance Score (KPS) of at least 60
• Patients should have stopped any anti-depressant medications by standard of care at least a month before enrolling in the trial
• Willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Prior treatment with other chemotherapy drugs for glioma
• Known hypersensitivity to Mirtazapine and 5-HT3 receptor antagonists
• Life expectancy of less than three months
• Pregnancy or breastfeeding.