Two of the most important things to know when deciding on which med is the best for a particular condition1: how likely is it to work and how long will it take.
The odds of a med working for a particular condition and how long it generally takes to work should be fairly easy to nail down, and not need to be summed up by the Internet shorthand YMMV (Your Mileage May Vary). Aside from it being hard enough to get an accurate diagnosis when brain cooties are involved, why is it so difficult to figure out if Zoloft is right for you and how long it will take for you to know that?
- Because no one is quite sure exactly what causes various conditions.
- Which is further complicated when everything is a spectrum disorder (e.g. bipolar 1, bipolar 2, all the others planned for DSM-V).
- And they’re never really sure about how Zoloft works in the first place.
- Plus, if you have more than one condition for which you’re taking one or more medications to treat, things get really complicated.
- None of which is helped by studies that produce contradictory results, if they aren’t questionable in the first place.2
Always remember: if your symptoms suddenly get a lot worse, call your doctor immediately. Any drug that makes your symptoms worse is a drug you probably need to stop taking as soon as possible.
See our page on the tests researchers use to measure the efficacy of medications, including during clinical trials to get FDA approval.
Like all SSRIs: anywhere from a couple days to over a month, although you’ll probably feel more awake and energetic, or at least start sleeping a little better, in two to four days. If you don’t feel any positive benefit after four weeks for depression alone, or two weeks for anxiety or depression and anxiety, then you should talk to your doctor about either another SSRI or, if you already tried another SSRI or an SNRI before and it didn’t work, trying a med that hits another neurotransmitter.
Like all SSRIs Zoloft has about a 40–50% chance of working, factoring in having to stop taking it for intolerable side effects. Those are actually decent odds for serious brain cooties like chronic, severe depression and social anxiety bad enough to keep you from holding a job.
Zoloft is better for conditions in the anxiety spectrum than those in the depression spectrum. Which is funny given how agitated and nervous it makes a lot of people feel. It’s not just any anxiety Zoloft is good for, but social anxiety/phobia, which really is different from other forms. So they aren’t lying to you all that much with those cheesy ads featuring the sad and lonely blob.
Zoloft works well for chronic depression (i.e. every day for months on end). Like Wellbutrin, Zoloft is especially good for depression defined by sleeping too much, eating too much, and withdrawing from the world. Zoloft is more likely to work for you if you have anxiety combined with depression, although Celexa is somewhat more likely to work for anxious-depression (defined as being severely anxious and severely depressed, either simultaneously or at different times).
5. Zoloft (sertraline) versus Other Antidepressants for its Approved Indications
Based upon the studies, the source material, and anecdotal evidence.
- Celexa vs. Paxil vs. Zoloft - which is better for medication compliance? Getting people to stay on their meds is essential in getting them to work. That seems obvious, but all the clinical trials in the world don’t mean shit if someone won’t get a refill. This study looks at just that, which med gets the most first refills for approved treatments: depression, social anxiety, and PTSD. The winner: it’s a statistical tie between Zoloft and Celexa, with 54.70% and 54.49% of people taking them getting refills. Given the size of the study - over 14,000 people - Paxil’s first refill rate of 50.99% is significantly poorer, but isn’t overwhelmingly so.
- Celexa vs. Paxil vs. Zoloft - which med do people stay on longer? This is an indicator of which one generally sucks the most, not which is the most successful, as this is for people who still needed treatment. 14,933 people with depression, PTSD, or social anxiety disorder all taking brand and not generics. The results: Paxil sucks the most, Celexa sucks the least.
- Celexa and Effexor are better for depression, including depression with anxiety, than Zoloft.
- Zoloft is better than Luvox,3 as are most other SSRIs.
- There’s not much difference in efficacy as far as Paxil, Lexapro, and Prozac are concerned, although Lexapro generally sucks less than Zoloft, while Zoloft tends to suck less than Paxil and Prozac. One study found if you’re anxious and jittery Zoloft is more likely to work than Prozac, but that was done before everything but Luvox was on the market.
- There aren’t enough data as far as Cymbalta vs. Zoloft is concerned, but my money is on Cymbalta. Dual-action antidepressants are usually better than single-action, and whatever affect Zoloft has on dopamine and sigma opioid, it’s not enough to make much of a difference in depression spectrum disorders, other than lessening some side effects (weight gain, sexual dysfunction, triggering mania) and worsening others (sweating, nausea and other tummy troubles, having a dysphoric mania when it does trigger mania).
- Zoloft vs. Celexa vs. placebo Over 300 patients with MDD in this double-blind study took Zoloft, Celexa or a placebo for 24 weeks. Celexa was the clear winner, especially with anxiety symptoms. Zoloft’s main problem: the GI side effects sucked too much, and lots of people in the Zoloft group dropped out by week eight.
- Zoloft vs. Celexa for depression. 50 people taking Zoloft vs. 50 people taking Celexa for six weeks. The results: Celexa is still king of all antidepressants. It worked faster, better, and for more people.
- Zoloft vs. Celexa vs. placebo for depression. 323 people were randomized to take Zoloft, Celexa, or a placebo for six months in this double-blind study. The results: It may have been a statistical tie as far as how well Celexa and Zoloft worked for depression and how they beat the placebo, but Celexa worked faster, worked better for anxiety, and sucked less. No numbers in the abstract, but Zoloft wasn’t statistically superior to placebo on the Hamilton anxiety scale.
- Zoloft vs. Celexa when prescribed by primary care physicians for depression. 400 people in this double-blind, 6-month-long study were given one or the other by their PCP. The result: Celexa was somewhat, if not statistically significantly better.
- Zoloft vs. Prozac for severe depression or anxious depression. This was one big-ass study. Actually they pooled the data from five double-blind studies. They had a total of 1,088 people, with 654 considered anxious-depressed and 212 with high severity depression. The abstract doesn’t define “high severity” depression, but it was probably based on HAM-D score. The results: Zoloft barely wins, but has a statistically significant advantage among the “severely” depressed.
- Zoloft vs. Prozac for depression. 118 people took Zoloft, 120 took Prozac for six months. The results: Although no numbers were given, Zoloft worked better, and helped those who were taking it sleep better as well.
- Zoloft vs. Prozac for depression, which works better and costs less? 116 people took Zoloft and 115 people took Prozac for six months. The results: No difference in how well they worked, but the people taking Prozac saw their doctors more often, and Prozac cost a lot more.
- Zoloft vs. Paxil vs. Prozac for depression. 573 people being treated by primary care physicians (PCPs) are randomly assigned one of the three SSRIs. If it didn’t work or suck too much over the course of 9 months they got to switch to another med that isn’t one of these. The results: Zoloft wins, but is barely more effective and marginally sucks less. There is absolutely no difference between Paxil and Prozac.
- Zoloft vs. Paxil vs. Prozac for anxious depression. 108 people with major depression with severe anxiety were randomly given one of the three meds for however long this study lasted. The results: a three-way tie. The only difference was Zoloft and Prozac started working in a week.
- Zoloft vs. Lexapro for depression. Double blind study with 212 people over 2 months. The results: Lexapro was barely, but not statistically significantly, more effective.
- Zoloft vs. Paxil for depression with personality disorder. 176 people took Zoloft and 177 took Paxil for six months. The results: For one thing, taking SSRIs for six months works a hell of a lot better than taking them for only two or three months. Another useful piece of information (that shows up in other studies): if nothing at all happens in two weeks, you may as well forget whichever one you’re taking. Otherwise Zoloft was somewhat better and sucked noticeably less.
- Zoloft vs. Paxil for delusional depression. A small, short study - 46 people and six weeks - but Zoloft kicked Paxil’s ass. Zoloft worked for 75% of people taking it, Paxil worked for only 46%, and 41% of people taking Paxil dropped out because of side effects.
- Zoloft vs. Effexor vs. Wellbutrin - which is most likely to make you manic? 174 people with bipolar 1, 2 or NOS in the depressive phase were prescribed appropriate, flexible dosages of one of the three ADs along with whatever mood stabilizer they usually take. The results: Effexor is the most likely to induce some form mania. 15% of people who took it switched to full-on bouncing off the ceiling mania vs. 7% of those who took Zoloft and 4% of those who took Wellbutrin. For any form of mania it was Effexor 31%, Zoloft 16%, Wellbutrin 14%. For people with rapid cycling the ranking is the same, but they use obtuse statistics numbers. People susceptible to rapid cycling were no more or no less likely to become manic than those who aren’t. Unfortunately no data are given regarding mania symptoms.
- Zoloft vs. Wellbutrin SR vs. Effexor XR for depression after Celexa didn’t work. Which AD is the best second choice after Celexa? According to this decent-sized (727 people, 239 took Wellbutrin SR?, 238 took Zoloft, and 250 took Effexor XR) study the winner is: Effexor by a nose, with Wellbutrin a close second. They both worked better and sucked less than Zoloft, but Zoloft wasn’t that far behind. Although when you’re looking at remission rates of 20–25% they’re not all that fantastic in any event.
- Zoloft vs. Effexor XR for depression. Since Zoloft might affect dopamine enough to consider it a dual-action serotonin and dopamine reuptake inhibitor, someone thought comparing its efficacy with Effexor, which is a serotonin and norepinephrine reuptake inhibitor (SNRI), was only fair. So, 82 people took Zoloft, 78 took Effexor XR in this 8-week, double-blind survey. The result: Effexor won as far as how many people it worked for. The abstract doesn’t tell us how well each one worked or how many people had to quit taking them due to side effects.
- Zoloft vs. Effexor XR for depression, and which discontinuation symptoms suck less. Really? You’re comparing Effexor with Zoloft? Not Paxil, not Cymbalta, not even Luvox with its super-short half-life? The results: Effexor XR sucked a lot more when the people in the study stopped taking it, otherwise there wasn’t much difference. How much grant money did you get for that? How much came from Pfizer? That’s what I want to know.
- Zoloft vs. Celexa - which one costs your HMO more? Who cares about efficacy, this is what it often comes down to. Back in 1999 dollars it was $931 per patient for Zoloft vs $1,035 per patient for Celexa. That probably explains why they had 15,222 people taking Zoloft and and 3,175 taking Celexa. The conclusion sums up their thinking:
Despite potential cost savings due to a lower acquisition cost, initial treatment of depression with citalopram was associated with higher depression-related charges than was sertraline in the population studied.
- Zoloft vs. Lexapro - which costs less to treat depression? The HMO bean-counters have decided that over six months it costs $919 dollars to treat someone with Lexapro and $1351 to treat them with Zoloft.
- Zoloft vs. Lexapro vs. Effexor vs. the brain-derived neurotrophic factor (BDNF) hypothesis of depression. A recent hypothesis of what causes depression and how meds fix it involves how much BDNF we have floating around and the effect meds have on it. The results: while all the depressed people in this study had lower amounts of BDNF than the
professional guinea pigshealthy control subjects, the meds acted very differently. Zoloft increased it after five weeks, Effexor took somewhere around six months to change it, and Lexapro didn’t affect it at all. Yet all three were about equally effective in treating depression. So much for that idea.
Zoloft vs. TCAs.
As far as efficacy is concerned, there’s not much difference. Zoloft sucks a hell of a lot less, and is far easier to keep taking than TCAs, so taking those into account Zoloft a clear winner.
- In fact, the bitching about side effects and difficulty of medication compliance (combing side effects with having to take TCAs 2–3 times a day vs. once a day for Zoloft) is bad enough that one hospital found brand-name Zoloft to be slightly cheaper to use than generic TCAs.
- Although one study found that Zoloft works better and sucks less for women, while TCAs work better and suck less for men. While nothing actually confirms that, in fact , when I looked at studies with full text or demographic data in the abstracts, combined with some of the reports, I think they might be onto something. At least as far as Zoloft is concerned.
- Zoloft vs. Tofranil (imipramine) for depression and panic disorder. 138 people took Zoloft, 69 took imipramine. For some reason women outnumbered men 3–1 in this study. The results: a tie. Zoloft sucked a lot less, otherwise the numbers were almost identical.
- Zoloft vs. Tofranil (imipramine) vs. various personality disorders for chronic major depression. No, I wrote that correctly. Read the self-defeating abstract for yourself and you’ll understand what I mean.
- Zoloft vs. imipramine for non-melancholic depression. “Non-melancholic” is another term for “exogenous” - depression caused by something in your life and not because your brain is messed up. Although exogenous tends to be out of proportion, but that’s splitting DSM hairs. The results: Zoloft clearly won this one. It was more effective for more people, kept more of them depression-free after they stopped taking it, and sucked a lot less.
- Zoloft vs. Tofranil (imipramine) for people 60 and older with severe depression. This small study - only 55 people - tracked the geezers for all of 6 weeks. The results: Imipramine was slightly more effective. As to which sucked less, that’s hard to figure out. More people taking imipramine dropped out due to intolerable side effects, but of those who completed the study, imipramine’s side effects sucked less than Zoloft’s.
- Zoloft vs. imipramine for chronic major depression with anxiety. Two hundred nine people took imipramine and 426 took Zoloft. 36%
liked the Mel Brooks moviemet criteria for high anxiety. The winner: people with anxiety, as more of them (66% vs. 54%) responded to either med. Otherwise the results were the usual: the two meds work the same, but Zoloft sucks less.
- Zoloft vs. imipramine to prevent relapse in chronic depression. 635 people were randomized to Zoloft or imipramine in a 2:1 ratio, given 12 weeks to get better and followed up after 16 weeks. Anyone who didn’t get better was given the other med. The results: a tie, except Zoloft sucked less. Gee, couldn’t see that one coming. I found this to be especially funny:
LIMITATIONS:The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates.
- Zoloft vs. desipramine for depression with OCD. C’mon, desipramine for OCD? Zoloft kicked its ass.
- Zoloft vs. amitriptyline for depression. 100 people took Zoloft and 105 took amitriptyline for six weeks. I’ll let you guess the results, because you won’t be wrong.
- Zoloft vs. imipramine vs. men vs. women for chronic major depression. So, does your plumbing make any difference as far as the Zoloft vs. imipramine contest is concerned? It might. 235 men and 400 women took one or the other for 3 months. Zoloft works better and sucks less for women, while imipramine works better, faster, and sucks less for men.
- Zoloft vs. imipramine vs. placebo for chronic depression - which keeps you from hurting yourself the best? Harm avoidance is apparently overlooked in a lot of studies. I can tell you from personal experience that people who are severely depressed are more than happy to put themselves in dangerous situations as a form of passive suicide. The clear winner here was Zoloft. Imipramine didn’t even beat the placebo.
Zoloft vs. imipramine vs. placebo for anger attacks during chronic depressionZoloft vs. imipramine vs. placebo for dysphoric mania in bipolar 2. This is from 1997, they didn’t know about dysphoric mania and bipolar 2. The results: imipramine was somewhat better, which isn’t surprising given how TCAs work.
- Zoloft vs. clomipramine for depression. Another TCA, another tie. This time the TCA’s side effects didn’t suck all that much more than Zoloft’s.
- Low dosage Zoloft vs. really low dosage Elavil (amitriptyline) for depression in people with Parkinson’s. At least this tiny study ran for three months. 16 people took 50 mg of Zoloft, 15 took 25 mg of amitriptyline. The results: Pretty much a tie, and neither did squat for the Parkinson’s symptoms.
Zoloft vs. other meds. This is way too random to pin down.
- Zoloft vs. reboxetine for depression. This was a small study of 41 people, 20 on reboxetine 21 on Zoloft. The results: Hard to say. Reboxetine is more effective and works faster, but sucks more - the one person who dropped out was in the reboxetine group. By the time the study was done both meds worked for about 80% of the people in each group. Turkish language version of the study is here.
- Zoloft vs. moclobemide for atypical depression. In this double-blind study 197 people took either Zoloft or the MAOI moclobemide for three months. The results: Zoloft was significantly better. That is surprising, as MAOIs are usually the best meds around for atypical depression. Zoloft worked better (HAM-D score decreased from 35.9 to 14.5 in the Zoloft group vs 36.3 to 16.1 in the moclobemide group) for more people (77.5% vs. 67.5%). Zoloft also worked better for anxiety, sleep, and a few quality of life categories.
- Zoloft vs. psychotherapy vs. Zoloft and psychotherapy for chronic moderate depression (dysthymia). Although not approved for dysthymia, SSRIs are used for it all the time and it’s close enough. The results: Zoloft alone worked best, followed by Zoloft + therapy. Zoloft alone kicked interpersonal psychotherapy’s ass, but maybe they just like drugs up in Canadia.
- Zoloft vs. Solian (amisulpride) - which works faster for depression? Solian (amisulpride) is an atypical antipsychotic (AAP) available in Australia, the EU and other European countries, but not the US. In Italy it’s also approved to treat depression. The results: Solian works a lot better a lot faster. It takes Zoloft three months to catch up.
- Zoloft vs. Valdoxan (agomelatine): which one helps you sleep better in depression with anxiety. Since Zoloft is pretty good at helping people with anxious depression sleep, why not compare it with a melatonin agonist? 154 people took Zoloft, 159 took Valdoxan for six weeks. The results: Valdoxan (not available in the US, or many other places) makes you sleep a hell of a lot better, and that seems to help with depression and anxiety caused or exacerbated by insufficient and/or crappy sleep.
- Zolft vs. St. John’s Wort for depression. A randomized, double-blind study run by real doctors involving people with real depression. The results: Both were equally effective, but St. John’s Wort sucked less. What? Some herb you can get at Ye Olde Suplement Shoppe works as well as real medicine? Not quite. They didn’t use ground up St. John’s Wort or even random St. John’s Wort extract. They used pharmaceutical-grade Hypericum extract imported from Germany, which is sold in, you know, pharmacies. And while the Hypericum generally sucked less, 4 people were withdrawn from the study by their doctors due to drug-induced side effects, including suicidal ideation and drug-induced mania, compared with one person taking Zoloft. And while the Hypericum sucked less, it didn’t suck that much less, and has side effects comparable to any antidepressant on the market.
- Here’s another one pitting Zoloft against Hypericum extract. The objective of the study totally gives away the desired outcome, “to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression.” Right. Give Zoloft to people who aren’t depressed enough to need real medication, and see if Hypericum doesn’t fail when comparing the results. The results being a complete tie, with Hypericum sucking somewhat less.
- Zoloft vs. extended-release Desyrel (trazodone) for depression. This is a weird one. I didn’t think anyone still used trazodone as a primary antidepressant. Oh, wait, this study was done in Italy. In Europe Desyrel is still used as an actual antidepressant and not just an add-on for sleep, or a sleep aid by itself. 62 people took Zoloft, 60 people took Desyrel (trazodone) XR in this double-blind, double-dummy4, 6-week study. The results: a tie. Although people in the trazodone group slept a lot better. Big surprise there.
- Zoloft vs. Mirapex for depression in people with Parkinson’s. Did these people have a grudge against Zoloft or something? Sure, the people with Parkinson’s didn’t have any movement problems, but still. The results: Mirapex (pramipexole) kicked Zoloft’s ass from Napoli to Pfizer HQ and back.
- Zoloft vs. Remeron ODT for depression. 345 people in this 8-week long, double-blind study took either Zoloft or the then-new Remeron orally disintegrating tablets (ODT - about the only way you can get Remeron most places these days). The results: Remeron worked faster, but eventually they were equality effective. Zoloft sucked less in what people usually consider the most important AD side effects: weight gain and sexual dysfunction.
Although Zoloft tends to work better for anxiety, especially social anxiety, than depression, there aren’t nearly as many comparisons with other meds for anxiety disorders. Probably because Zoloft is better for social anxiety disorder/phobia (SAnD), while all the other meds with approvals to treat anxiety disorders are better than Zoloft.
- Zoloft vs. cognitive behavioral therapy (CBT) for late-life anxiety disorders. The abstract is totally vague. All I know is it lasted a year, and they used the Hamilton Anxiety Rating Scale and Worry Domain Questionnaire. The results: shut-up and give gramps his pills.
- Paxil vs. Zoloft for GAD. This was a tiny (55 people), two-month long, double-blind study. The results: a total tie.
- Zoloft vs. Serzone (nefazodone) for PTSD. Even smaller than above. 37 people took Zoloft or nefazodone for three months. The results: One worked faster, but the abstract isn’t telling me which. Otherwise it was a draw.
- Zoloft vs. Effexor XR vs. placebo for PTSD. 538 people took one of the three for three months. The results: Effexor XR won, sometimes doing much better than Zoloft, sometimes only doing a little better. Placebo did OK.
- Zoloft vs. self-administered cognitive behavior therapy (SCBT) vs. placebo vs. Zoloft and SCBT vs. placebo and SCBT. 251 people were given some permutation of the above for three months. The results: the combination of SCBT and Zoloft was the winner, and everything else didn’t do much good.
- Zoloft vs. cognitive behavioral group therapy (CBGT) for OCD. 28 people took Zoloft, 28 people went to group therapy for three months. The results: therapy kicked Zoloft’s ass. CBGT worked better for more people, including complete remission for 8 people vs. 1 for Zoloft.
- Zoloft vs. habit reversal training (HRT) vs. Zoloft and HRT for trichotillomania. At least someone cared enough about trichotillomania, chronic hair pulling, to do a small study. The abstract is pretty vague, but it looks like only the two combined actually work after 22 weeks.
- Premature ejaculation cage match! Luvox vs. Paxil vs. Prozac vs. Zoloft vs. placebo. Sixty guys with a hair trigger (one minute or less) were given a stopwatch (that probably did wonders for everyone’s mood) and either a placebo or an SSRI for six weeks. The results: Luvox is worthless. While the average for the rest was around two minutes, Paxil worked best, followed by Prozac and Zoloft. I can’t tell if they got to keep the stopwatches, let alone what effect using a stopwatch during sex had on delaying ejaculation.
- Zoloft vs. Celexa for premature ejaculation. 40 men took Celexa and 40 took Zoloft for two months. The results: a tie. They used a scale instead of time, so I have no idea how well each med really worked.
- Topamax works better than Zoloft for nocturnal binge eating, but Zoloft sucks a lot less.
- Zoloft vs. Prozac for binge eating.
- Zoloft vs. nortriptyline for postpartum depression. This study looked specifically at sexual function. The result: a tie.
- Zoloft vs. Prozac for undifferentiated somatoform disorder (USD). 45 people, 28 took Prozac (fluoxetine) 17 took Zoloft. The results: a tie.