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The symptoms appear with rapid discontinuation of one of these drugs, and can include dizziness, disturbance of balance, headache, nausea, insomnia, and vivid dreams.Others can include sensations of tingling or numbness, ‘electric-shock’-like sensations, and irritability, with some case reports of hallucinations.Slower-acting drugs, like fluoxetine, may be less likely to cause discontinuation symptoms, but the evidence for this is weak as well.

This analysis was criticized by Donald Klein, who noted that suicidality, that is suicidal ideation and behavior, is not necessarily a good surrogate marker for completed suicide, and it is still possible that antidepressants may prevent actual suicide while increasing suicidality.

There is less data on fluoxetine than on antidepressants as a whole.

For the above analysis on the antidepressant level, the FDA had to combine the results of 295 trials of 11 antidepressants for psychiatric indications to obtain statistically significant results.

Considered separately, fluoxetine use in children increased the odds of suicidality by 50%, Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in the children and adolescents on fluoxetine as compared to the ones on placebo.

According to the MHRA data, for adults fluoxetine did not change the rate of self-harm and statistically significantly decreased suicidal ideation by 50%.

In some cases, use of dextromethorphan-containing cold & cough medications with fluoxetine is advised against, due to fluoxetine increasing serotonin levels, as well as the fact that fluoxetine is a cytochrome P450 2D6 inhibitor, which causes dextromethorphan to not be metabolized at a normal rate, thus increasing the risk of serotonin syndrome and other potential side effects of dextromethorphan.

Sexual dysfunction, including loss of libido, anorgasmia, lack of vaginal lubrication, and erectile dysfunction, are some of the most commonly encountered adverse effects of treatment with fluoxetine and other SSRIs.

While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively inquires about sexual problems suggest that the incidence is Antidepressant discontinuation syndrome is an adverse effect of second generation anti-depressants, including fluoxetine.

In pregnancy, fluoxetine is considered a category C drug.

Evidence supporting an increased risk of major fetal malformations resulting from fluoxetine exposure is limited, although the Medicines and Healthcare Products Regulatory Agency (MHRA) of the UK has warned prescribers and patients of the potential for fluoxetine exposure in the first trimester (during organogenesis, formation of the fetal organs) to cause a slight increase in the risk of congenital cardiac malformations in the newborn.

However, a systematic review and meta-analysis of 21 studies – published in the Journal of Obstetrics and Gynaecology Canada – concluded, "the apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias.

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