Exhibit (a)(1)(E)
OFFER TO PURCHASE FOR CASH
ALL OUTSTANDING SHARES OF COMMON STOCK
OF
CYPRESS BIOSCIENCE, INC.
AT
$4.25 NET PER SHARE
BY
RAMIUS V&O ACQUISITION LLC,
A WHOLLY OWNED SUBSIDIARY OF
RAMIUS VALUE AND OPPORTUNITY ADVISORS LLC
September 15, 2010
To Our Clients:
Enclosed for your consideration is an Offer to Purchase dated September 15, 2010 (the “Offer to
Purchase”) and the related Letter of Transmittal (which, together with any amendments or supplements thereto,
collectively constitute the “Offer”) relating to the Offer by Ramius V&O Acquisition LLC, a Delaware limited
liability company (“Purchaser”) and a wholly owned subsidiary of Ramius Value and Opportunity Advisors LLC,
a Delaware limited liability company (“Ramius”), to purchase all issued and outstanding shares of Common
Stock, par value $0.001 per share (the “Shares”), of Cypress Bioscience, Inc., a Delaware corporation
(“Cypress”), at a price of $4.25 per Share, net to the seller in cash, without interest and subject to any required
withholding of taxes (the “Offer Price”), upon the terms and subject to the conditions set forth in the Offer to
Purchase and the related Letter of Transmittal.
If a stockholder desires to tender Shares pursuant to the Offer and such stockholder’s Share Certificates
(as defined in Section 1 — “Terms of the Offer; Expiration Date” of the Offer to Purchase) are not immediately
available or the procedures for book-entry transfer cannot be completed on a timely basis or time will not permit
all required documents to reach the Depositary (as defined in “Summary Term Sheet” of the Offer to Purchase)
prior to the Expiration Date, such Shares may nevertheless be tendered according to the guaranteed delivery
procedures set forth in Section 3 — “Procedures for Accepting the Offer and Tendering Shares” of the Offer to
Purchase. See Instruction 2 of the Letter of Transmittal. Delivery of documents to the Book-Entry Transfer
Facility (as defined in