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For better or for worse, a great many people take medication for depression or anxiety which would be truly bad news to combine with alcohol. I was under the impression a celebrant MUST get drunk enough to not be able to identify Mordechai from Haman, but was not sure whether this is merely an optional custom or mandatory portion of observance. Can someone taking said medications opt out of drinking during Purim?

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Not just MAY. MUST avoid drinking on Purim. Even a Biblical mitzvah for a case like this, one must avoid and not put oneself in danger. (There is a commandment to safeguard one's life.) Certainly for a rabbinic mitzvah. –  josh waxman Nov 15 '13 at 1:09
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2 Answers

ABSOLUTELY.

DO NOT DRINK IF IT IS MEDICALLY CONTRAINDICATED!! NEVER EVER EVER!!

Immediately after the statement about "obligation to drink on Purim", the Gemara tells a tale of one rabbi who got drunk and very nearly killed someone. Most rabbis say that's just a cautionary note to moderate your drinking, but the Baal HaMaor says the Gemara is refuting the previous statement, i.e. there is no obligation to drink at all. We try to accommodate the other opinions if it's not too difficult, but if someone has reason not to drink, they can certainly rely on the Baal HaMaor.

But putting aside the Baal HaMaor: If a person needs antidepressants, that's a potentially life-threatening condition and (unless both their doctor and their rabbi says otherwise) they can violate Pesach, Yom Kippur, Shabbos, etc. if needed to take them. They absolutely, most certainly can and should be passive about this rabbinic quasi-commandment. They are obligated to preserve their health and not do anything that could put themselves into the emergency room.

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Although your point about not endangering oneself is correct and well-made, your paragraph about the general obligation of drinking on Purim is not fully correct. The Ba'al HaMa'or, Ran, Orchos Chayim, and Rabbeinu Efrayim (and the Rambam as understood by the Aruch HaShulchan) all agree that the gemara rejects ad d'lo yada due to the story with Rabba. Nonetheless, they would presumably agree (and some state this explicitly) that some amount of drinking is necessary to fulfill y'mei mishteh v'simcha (again, that is of course not applicable for someone on medication as described in the OP).. –  Fred Nov 14 '13 at 20:35
    
...Likewise, even some rishonim that accept ad d'lo yada, interpret it to indicate that drinking should be moderate (e.g. Tosafos) or can be moderate (e.g. Ra'avya). Many acharonim also come down on both sides of whether the gemara accepts or rejects ad d'lo yada, and how to interpret the consequent halachic implications. –  Fred Nov 14 '13 at 20:36
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I think the most succinct words of wisdom on this subject are from Kitzur Shulchan Aruch:

However, one who has a weak constitution, and also one who knows himself, that by this (excessive drinking) he would treat lightly, Heaven forbid, some commandment, a blessing, or a prayer, or will come, Heaven forbid, to irreverence, it is best (for him) not to get drunk. (Thus) and ''all your actions will be for the sake of Heaven.''

Note in that quote the "excessive drinking" is the translators interpolation. Really he is talking about any level of drinking that could bring a person to miss a commandment, it all depends on the person. Avoiding dangers to your health is most definitely a commandment.

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