Antidepressant Treatment Strategies For The First-Timer

In previous newsletters, I have often written about antidepressants. Ten percent of Americans use them, and I field more questions about these drugs than any other medication category in my nationwide seminars and trainings.

What I haven’t addressed though is how to begin antidepressant treatment. I’m speaking here of the first-time user — someone who has contemplated antidepressant use and has decided to go forward, usually after an evaluation conducted by a qualified health or mental health professional. Of course, there’s no one way to initiate antidepressant treatment, so for those just starting out, it’s worth becoming a fully-informed consumer, knowing what to expect and how treatment is likely to proceed.

There are no definitive, authoritative practice guidelines for initiating antidepressant treatment. None. So in the absence of a “this is THE way to go” approach, prescribers and consultants like myself develop our own algorithms for getting patients started. Here are mine:

I begin with this: All antidepressants are equally effective. For those suggesting for example, that the older tricyclic antidepressants (amitriptyline, nortriptyline, etc.), may be more effective for melancholic, vegetative depression types, I’ll concede this has merit. But I’m referring here to the broad range of applicability across a number of symptom spectrums, in which case, I see no measurable differences. So assuming that these agents are equally effective, I concentrate on factors other than efficacy to get patients started.

  • How the depression presents.
  • Co-occurring disorders
  • Prior history
  • Side effects
  • Duration
  • Dosing


How the depression presents.
 No antidepressant as a single agent will successfully address all common symptom domains such as anxiety, insomnia, agitation, lack of motivation, appetite, and poor concentration problems, so I do’t focus on these at first. Managing a constellation of symptoms is better facilitated through dosage adjustment or augmentation. Instead, I’l focus on the characteristics of the depression. The two most common manifestations are the “low-drive” type and the “high distress” type. For the low-drive depressed patient, the activating and energizing properties of Wellbutrin would be an acceptable initial choice, whereas the “quieting” effect of an SSRI like Lexapro would be a better choice for the anxious, depressed patient.

Co-occurring disorders. Here’s where the SSRIs tend to shine. The selective serotonin reuptake inhibitors (Prozac, Zoloft, Paxil, Celexa, Lexapro) are effective for almost the entire anxiety spectrum — panic, generalized anxiety, social anxiety, as well as anxiety associated with OCD and PTSD. These agents are also effective in managing certain eating disorders, anger and irritability. Cymbalta is my go-to antidepressant for pain conditions and depression. Wellbutrin aids in smoking cessation and ADHD symptoms as well as depression.

Prior history. The focus of this article is on the patient with no prior antidepressant experience. What if the patient were to report that a close family member responded well to a particular antidepressant? This question is largely unexamined in the clinical literature, so there is virtually no direction here. So what to do? I’ll focus on the low-drive vs. high-distress factors, and in consultation with the patient, decide on a drug, get started and assess from there.

Side effects. A lot can be made of antidepressant side effects, and I’ve had patients complain of just about everything. The truth is that most antidepressant side effects are transient and will abate fairly quickly, but there are 2 exceptions: weight gain and sexual problems. Paxil and Remeron (a go-to for insomnia) can both cause significant weight gain. All other antidepressants are weight-neutral, maybe a 5 pound gain tops.

Duration. The optimal time frame for an antidepressant trial is murky at best and it comes down to whom you ask. Keep in mind, I’m talking about a “trial” here, not how long someone eventually stays on an antidepressant that is working for them on some level. My guideline for an initial trial: 4-6 weeks. However many patients do eventually respond when staying on the drug for 8-10 weeks.

Dosing. Here’s how I advance the dosing issue: First, begin with 1/2 of the minimum recommended effective dose (e.g. Prozac 10mg). Then if the patient is tolerating this, increase to the minimum effective dosage (e.g. Prozac 20mg) after one week. If there is no improvement after a 3-week period, another bump up is warranted. Then evaluate at the 6-week mark. If still no improvement, it’s time to switch or augment.

antidepressantsMy starting five. 

  1. Prozac
  2. Lexapro
  3. Cymbalta
  4. Wellbutrin
  5. Remeron

Prozac and Lexapro, as SSRIs, provide the broadest array of possible benefits, particularly for accompanying anxiety syndromes. These antidepressants have few drug-drug and drug-food interactions, are extremely well tolerated, and are incredibly safe in overdose with very manageable side effects — apart from sexual dysfunction.

Cymbalta shines in those with depression and concomitant pain conditions — including chronic pain, fibromyalgia, skeletal pain and diabetic neuropathy.

Wellbutrin, like Prozac and Lexapro, has very few drug interactions. (It is contraindicated in anyone with a seizure history). I particularly like it because it is absent of sexual side effects and weight gain. And it gets depressed people moving because of its energizing properties.

Remeron may be the best agent I’ve encountered for depression accompanied by insomnia and loss of appetite. Weight gain and next-day hangover or feelings of excessive sedation are this drug’s main negatives, but can be attenuated through dosage adjustment or taking the drug earlier in the evening.

The challenge for both prescriber and patient when it comes to first-time antidepressant use is the absence of telltale history to utilize as a guide. So the old adage of “starting low and going slow,” accompanied by consistent monitoring and a willingness on the patient’s part to hang in there and not lose faith in the treatment process, are all key to achieving success.


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Attribution Statement:
Joe Wegmann is a licensed pharmacist & clinical social worker has presented psychopharmacology seminars to over 10,000 healthcare professionals in 46 states, and maintains an active psychotherapy practice specializing in the treatment of depression and anxiety. He is the author of Psychopharmacology: Straight Talk on Mental Health Medications, published by PESI, Inc.

To learn more about Joe’s programs, visit the Programs section of this website or contribute a question for Joe to answer in a future article: joe@thepharmatherapist.com.