The results from this study support that citalopram, in a dose as low as 10-mg per day can significantly improve hot flash activity, with virtually no toxicity. This is contrary to the results of Suvanto-Luukkonen.13
In their 9-month study, the authors reported that there were no statistically significant differences in hot flashes between citalopram, fluoxetine, or placebo. However, this trial did not include a baseline week period to measure hot flash activity.26
The authors used hot flash information from day 1 as baseline, yet study medication also began on this day. This is problematic in that it has been demonstrated in a study evaluating venlafaxine, that on the very first day, hot flashes decreased by 30% compared to baseline. This issue is discussed in detail in two previous manuscripts.26,27
Clinically, it is reasonable to begin a patient on a 10-mg/d dose for a week or two and then determine whether titration up to 20 mg per day would be further beneficial. These data do show that although there was not a significant difference in hot flash reduction between doses of citalopram, a significantly beneficial impact on broader daily activities required 20 mg/d. The 30 mg/d dose was associated with a tendency for more toxicity with little increased hot flash improvement and, therefore, is not recommended.
It may seem surprising that overall mood disturbance as measured by the POMS was not significantly better in the citalopram arms since it is a mood modulator. However, participants in this study were recruited based on hot flashes, not mood disturbance. It could be that the lack of significance on mood reflects the lack of variability in this domain as well as floor effects. It is also important to note that the doses used to manage hot flashes are lower than those used to manage depression and therefore, may not produce an effect size large enough to be statistically significant. Both anger/hostility and tension/anxiety, however, were significantly impacted, being two things that are associated with effects of hot flashes.28
In addition, these findings provide further support that the decrease in hot flashes is likely not simply the result of overall mood improvements.
When evaluating treatments for hot flashes, it is important to know how much of a decrease in hot flashes is truly beneficial for women, namely, how much of a decrease would positively impact other areas of life. This study provides novel data related to this issue. Based on the results from the HFRDIS, a daily reduction of approximately 50% is needed in order for women to perceive general quality of life improvements. This reduction is more than what a placebo generally offers (25% to 30%) and therefore, may be one additional way to ascertain real versus placebo effects of an intervention.
The most feared adverse effects of SSRIs are negative sexual adverse effects. Due to the coexistence of hot flashes and sexual changes as a result of menopause, treatment for hot flashes with SSRIs may be particularly worrisome. There are currently no long-term studies with low-dose SSRIs for hot flashes that reveal the true incidence of sexual changes. Drug references for citalopram list a 1% to 6% incidence of sexual dysfunction, which, for females, includes 1% of patients noting anorgasm and 1.3% noting a reduced libido. Ejaculatory issues and impotence are a bit more common in men with 4% and 3% incidences, respectively.29
The incidence of sexual changes related to SSRIs is further complicated by the comorbidity of depression in the population from which the data are derived. This study does not provide any data to suggest that short-term changes in sexual function occurred due to citalopram. More research on long-term effects of antidepressants, in doses needed to treat hot flashes, is warranted.
As hot flashes can negatively impact some areas of life, such as sleep, it is important that health care providers assess both the positive and negative effects of each hot flash intervention for individual patients to make sure that the symptom improvement is not countered by other unwanted adverse effects. The improvement in the area of hot flashes interfering with sleep was profound on citalopram, with a 32-point improvement on a 100-point scale for the 20 mg/d dose.
Strengths of this study include the fact that it is a dose finding trial, only the third such trial done with the antidepressants. One limitation of this study is that it was 7 weeks long. While we have shown that effects of gabapentin and other effective antidepressants plateau between 4 and 12 weeks,30
long-term control of hot flashes or adverse effects with citalopram cannot be determined from this study.
Finally, consistent with a previous pooled analysis, efficacy of citalopram did not differ based on etiology or breast cancer history.31
Thus, in total, these data demonstrate that citalopram decreases hot flashes to a similar degree to what has been seen with venlafaxine, paroxetine, gabapentin,26
and is, therefore, another option for women in managing hot flashes.26,27
However, citalopram may have some advantages over the other agents. Citalopram, unlike paroxetine, can be given with tamoxifen.33
As little as 10 mg/d of citalopram is needed for a 46% reduction in daily frequency. This, coupled with the minimal adverse effect profile at this dose, makes this particularly useful for women who have difficulty tolerating pharmacologic agents and appears to be more tolerable than either gabapentin or pregabalin (although this would need confirmation ideally with a head to head trial). Citalopram is also only taken once per day and is available generically. Therefore, it has the dosing advantage of venlafaxine, extended release, without the cost.