Depression ? caused by medication ? Jan 2009

[Guest guest]

Good Afternoon

If anyone has had a sudden or slow build up of depression since

diagnosed of CML and then it would also be that you commenced your

CML medication at the same time.

Has anyone considered the condition maybe contributed by your

medication.

It is only something that your specialist can evaluate - however

it is food for thought.

What is your experience ?

An abstract from Medscape that maybe of interest to you all

discussing this very topic.

Sue

_______________________________________________________________

Case Histories of Severe Depression With Imatinib and Dasatinib

Nick Mulcahy

January 16, 2009

— Seven patients receiving the tyrosine kinase inhibitors (TKIs)

imatinib (Gleevec, Novartis) or dasatinib (Sprycel, Bristol-Myers

Squibb) have experienced severe and treatment-related depression,

according to clinicians from the Dana-Farber Cancer Institute, whose

letter on the subject was published in the January 10 issue of the

Journal of Clinical Oncology.

The correspondence calls for routine screening for suicide ideation

and depressive symptoms in all patients being treated with the small-

molecule TKIs imatinib and dasatinib. The Dana-Farber clinicians also

call for dose-reduction and, if necessary, treatment discontinuation

as strategies to alleviate the depression.

TKIs have a " tolerable adverse-effect profile " that includes fluid

retention, diarrhea, cramps, and fatigue, note the authors, one of

whom, D. Block, MD, is chair of the department of psychosocial

oncology and palliative care at the Dana-Farber Cancer Institute, in

Boston, Massachusetts.

Dr. Block and her colleagues called TKI-associated depression " an

under-recognized small-molecule TKI effect. "

In an interview with Medscape Oncology, Dr. Block suggested that

clinicians may not have noticed depression in other TKI-treated

patients. " We know that diagnoses of depression are missed by

nonpsychiatric physicians the majority of the time, " she said.

A " striking pattern " exists in this series of 7 patients. " All were

coping well with their disease psychologically before

imatinib/dasatinib therapy, yet developed profound depression during

treatment, with many experiencing complete remission or improvement

of symptoms after dose reduction or drug discontinuation, " write the

authors of the letter.

TKI-associated depression was only noticed among patients taking

imatinib or dasatinib. However, " it is not inconceivable that similar

adverse effects may be seen with other TKIs, " write the authors. TKIs

share common mechanisms of action and have overlapping molecular

targets.

A spokesperson for Bristol-Myers Squibb, the makers of dasatinib,

also noted that the depression is not specific to 1 drug. " As the

letter points out, psychiatric disorders, including insomnia and

depression, are not specific to any one therapy and are manageable.

[Chronic myeloid leukemia] is a life-threatening disease and

treatments such as [dasatinib] have led to significant positive

advances for patients, " said Henry of Bristol-Myers Squibb in a

communication to Medscape Oncology.

Novartis, the makers of imatinib, did not respond to Medscape

Oncology about the letter and case reports of depression.

Imatinib is indicated for chronic myeloid leukemia and

gastrointestinal stromal tumors (GIST), and dasatinib is also

indicated for chronic myeloid leukemia, but in patients with

resistance or intolerance to previous therapy, including imatinib.

Both drugs are also indicated for use in patients Philadelphia

chromosome-positive acute lymphoblastic leukemia.

Imatinib and dasatinib are widely considered to have revolutionized

the treatment of both GIST and chronic myeloid leukemia.

Inconsistent Response to Depression Treatment

TKI-associated psychiatric symptoms responded inconsistently to

standard antidepressant treatment; according to the authors. " Most

cancer-related depressions are relatively responsive to low-dose

antidepressant medications and psychotherapy, and these TKI-related

depressions are not, " said Dr. Block.

Only a small minority of patients with cancer develops depression

related to their illness, she added. The depressions seen in this

series of patients was not disease-related, according Dr. Block.

" The treatment-associated depression we saw with the TKIs occurred in

temporal relationship to starting and stopping the drug, in patients

without a prior history or family history of depression, was less

responsive to treatment than usual depressions, and was unusually

severe, " she summarized.

In the event of TKI-associated depression, dose reduction may benefit

some patients. In severe treatment-refractory cases, discontinuation

of the suspect TKI should be considered, say authors of the letter.

The authors emphasized the importance of close and careful monitoring

of depression and suicide ideation. " Given the known elevated risk of

suicide in cancer patients, suicidal ideation should be treated as a

psychiatric emergency, with immediate referral to a psychiatrist for

assessment, " they write.

Prescribing Information Lists Depression as Adverse Effect

The prescribing information for both imatinib and dasatinib lists

depression as an adverse event. However, depression is not

highlighted with a warning or precaution/caution for either drug.

In a clinical trial of imatinib among newly diagnosed chronic myeloid

leukemia patients, depression (all grades) occurred in 14.9% of

patients, and grade 3/4 depression occurred in 0.5% of patients. In a

trial of adjuvant imatinib among GIST patients, depression (all

grades) occurred in 6.8% of patients and grade 3/4 depression

occurred in 0.9% of patients.

In the dasatinib prescribing information, depression is listed as

occurring in 1% to more than 10% of patients; no mention is made of

the depression grade.

Sample Story

The letter from the Dana-Farber clinicians details the 7 cases of

depression seen in their clinics, including the following abridged

version of 1 of the case reports.

A 55-year-old male with GIST, diagnosed in January 2000, underwent

complete resection, but the disease recurred in March 2001. He

was " coping well " with his metastatic cancer diagnosis, worked full

time, and ran 4 miles daily.

Within 5 months of being prescribed 800 mg/day of imatinib, the

patient developed new severe depression. He experienced decreased

libido, diminished attention span, disorganization of thoughts, and

intense feelings of hopelessness, helplessness, and demotivation. He

began to struggle in his corporate leadership role. Symptoms proved

refractory to standard therapy for depression. The imatinib dose was

reduced to 400 mg/day. The patient then reported an increase in

energy level with alleviation of depressed affect, which was

sustained for about 1 year.

Then, he again reported worsening depression, became periodically

tearful, and was unable to function at work. Eventually, imatinib

treatment was discontinued and he experienced prompt resolution of

depression.

Over the course of this man's illness, he had been challenged 5 times

with high-dose imatinib (600 to 800 mg/day), write the letter

authors. Each time, imatinib therapy precipitated depression. In

every instance but one, depressive symptoms diminished or resolved

completely with dose interruption.

Dr. Block has disclosed no relevant financial relationships. Those of

her coauthors are listed at the end of the published correspondence.

J Clin Oncol. 2009;27:312-313. Abstract