Prozac vs Wellbutrin SR vs Celexa: The Most Popular Antidepressants

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Product name Wellbutrin

from $2.03 to $1.39

Category Antidepressant
Active ingredient Bupropion hydrochloride
Avaliability In Stock
30 60 90 120

Drug Therapy of Depression

Depression is a curable disease. If there are grounds for believing that you suffer from depression, discuss it with your physician, psychiatrist or behavioral therapist. As a rule, depression is treated with anti-depressants which have innumerous variants on pharmaceutical market. In 1960-1980s the so-called tricyclic antidepressants and inhibitors of monoamine oxidase were the most popular. Nevertheless, new medications have been developed in the last ten years. They proved to be no less effective and with softer side-effects.

Drug-Therapy of Depression

Let us examine anti-depressants of third generation:

1. Selective serotonin reuptake inhibitors (SSRIs) influence mainly serotonin neurotransmitter.

They include:

  • Fluoxetine (Prozac, Sarafem);
  • Sertraline (Zoloft);
  • Paroxetine (Paxil);
  • Citalopram (Celexa);
  • Escitalopram (Lexapro);
  • Fluvoxamine (Luvox).

These medications are considered to be first-line anti-depressants, since they are safe, effective and are often prescribed by therapists.

2. Selective dopamine reuptake inhibitors, such as venlafaxine (Effexor), mirtazapine (Remeron), bupropion (Wellbutrin, Zyban) have a unique mode of action and are very efficient.

3. Selective norepinephrine reuptake inhibitors: atomoxetine, pizoxetine, reboxetine.


In this article, we’ll focus on the couple of medications: Celexa (citalopram) and Prozac (fluoxetine). Their mechanism of action is similar and connected with impact on 5-HT serotonin receptor. It is worth mentioning that selective serotonin reuptake inhibitors are relatively safe (they have the least number of side-effects) and very comfortable for treatment (on an outpatient basis). SSRIs are also distinguished by low toxicity (the risk of lethal outcome after intoxication or overdose is practically equal to zero), as well as by possibility to be used by patients who are not allowed taking tricyclics (heart beat disorder, urinary difficulty due to prostatic hypertrophy, angle-closure glaucoma).

Most SSRIs are prolongers and used in fixed dosage. Pharmacokinetics of divers representatives of this group has its peculiarities in accordance with patient’s age and general medical condition. Clinical trials have shown that SSRIs are efficient for the majority of depressive conditions, including anxiety, sleep disorders, psychomotor agitation and loginess.

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Clinical differences of Celexa and Prozac

  • Their clinical differences generally lie in elimination half-life (T1/2) and particularities of medicinal interactions. Fluoxetine half-life and the one of its active metabolite is around 330 hours, whereas other SSRIs have the index of 15-30hours. This indicator is very important if a patient switches from SSRI over the drug from another group. It is also essential for assessment of prognosis in case of adverse drug reaction development requiring immediate refusal of selective serotonin reuptake inhibitors. On the other hand, long-term elimination half-life allows increasing patient compliance and requires in some cases the drug intake every 2 or 3 days.
  • Medicines have different degrees of selectivity of serotonin reuptake inhibition. The most selective between these two medicines is Celexa. SSRIs inhibit cytochrome system P-450 in liver predetermining the possibility of pharmacokinetic interactions. Prozac inhibits CYP2 D6. On the setting of Celexa intake, the risk of interactions connected with P-450 inhibition is minimal.
  • Since SSRIs do not block cholinergic, histaminergic and adrenergic systems, they do not have side-effects connected with them. But due to activation of various subtypes of serotonin receptors, there may occur serotoninergic adverse drug reactions, such as nausea, diarrhea, low appetite, weight loss, anxiety, apprehension, sleep disorders, sexual issues. Characteristic to tricyclic antidepressants cardiotoxicity is absent with SSRIs which is important in case of suicidal overdose of the medicine. SSRIs proved to have the same effectiveness as tricyclics but for two exceptions: fluoxetine was much less effective than tricyclics with patients having the high rating according to Hamilton Depression Rating Scale.
  • Therapeutic effect of SSRIs is quite similar, excluding the fact that fluoxetine (Prozac) has a slow onset time.

Prozac (Fluoxetine)

Prozac-capsOne of the first selective serotonin reuptake inhibitors was Prozac. Since 1980s it has been actively applied for therapy of various disorders of depressive spectrum.  Besides, its positive effect was observed while treatment of bulimia. Fluoxetine is prescribed in dose of 20mg once a day in the morning. The dose is increased to 40-80mg if required. The medicine is well-absorbed for peroral prescription, demethylates in liver with production of inactive metabolites and pharmacologically active norfluoxetine.

Due to particularities of metabolism, the effect of Prozac is significantly influenced by hepatic functionality. It inhibits activity of hepatic cytochromes P4502D6. Hence, the remedy slows down metabolism of a number of psychotropic agents along with the increase of their concentration in liver and blood plasma which determines the possibility of toxic effects occurrence.

Maximal concentration of fluoxetine in blood is reached within six hours. It has the most positive elimination half-life period among all SSRIs which lasts 2-3 days, whereas the half-life period of its active metabolite, norfluoxetine is about 7-9 days. This fact provides advantage of Prozac in treatment of patients who may sometimes forget about the intake of regular dose. On the other hand, the procedure of Prozac substitution by other anti-depressants becomes rather difficult. In order to achieve stable concentration of active substance it takes several weeks. Regardless of anxiolytic effect, Prozac may enhance anxiety and agitation at the initial stage of therapy, since it has a disinhibiting effect.

In comparison with other selective serotonin reuptake inhibitors, Prozac eliminates the symptoms of depression considerably slower (within 2-3 weeks). Nevertheless, its final effect is analogous to the one of other medications of this class. It has been demonstrated that Prozac is equal to tricyclics according to its efficiency in removal of depression symptoms. At the same time, there is a point of view that Prozac is inferior to other SSRIs in its capacity to block the common manifestations of depression.

The first days of Prozac intake may be accompanied by nausea, headaches, distortion of vision, akathisia, skin allergies. Also, during Prozac intake, sexual issues have been observed.

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Celexa (Citalopram)

Celexa (Citalopram)Celexa has a considerably higher level of selectivity in regards to serotonin transmitters in comparison with transmitters of norepinephrine and dopamine. The medicine is prescribed in dosage of 20mg per day in the morning. For most patients this dose is the most effective. Maximal daily dose is 60mg.

Celexa practically doesn’t interact with other drugs and thus, it has an insignificant influence on activity of some hepatic enzymes (enzyme cytochrome P450). Therefore, this remedy is often used for therapy of depressive disorders developed because of somatic diseases.

Intra-medicinal interactions of Celexa are minimal. Under the influence of cytochrome P450 citalopram turns into two main metabolites: demetiltsitalopram and didemetiltsitalopram. These metabolites have pharmacological activity which is less than the one of citalopram itself. The half-life of citalopram is 30 hours. It is characterized by linear dependence of concentration in blood plasma according to dose in therapeutic interval. In order to treat severe depressions, the medicine’s dosage may be increased. Celexa is recommended to be taken in general medical practice for aged ill persons who have in cerebral stroke in the past medical history.

Patients taking citalopram have insignificant percent of men with disturbed sexual function. This is a side-effect which is relatively often met while prescribing the medications from SSRI group. Headache and nausea are the most frequent undesired effects after therapy with Celexa within the first two weeks of its intake.

Prozac vs Celexa

Comparison of these medications may be conducted according to the following criteria:

  • Intensity of effect: both Prozac and Celexa have moderately pronounced effects
  • Additional therapeutic effect: Prozac – disinhibiting effect, Celexa – anxiolytic.
  • Selectivity: Celexa has a higher level of selectivity. The difference in selectivity and intensity of influence on receptors is determinative for not only therapeutic effect, but also on presence of side-effects.
  • Depression setback: in equal conditions, depression setbacks are more frequently met after Prozac therapy than after the course with Celexa. Prozac has a disinhibiting effect and may enhance anxiety and psychic tension.
  • Side-effects: Prozac – moderately pronounced side-effects, Celexa – mildly pronounced side-effects. The most frequent side-effects are anxiety, agitation, insomnia, increased drowsiness, sexual disorders.

Wellbutrin SR vs SSRIs

Wellbutrin SR vs SSRIs1

Wellbutrin with its active component bupropion is a sole anti-depressant taking a double effect on the reuptake system of norepinephrine and dopamine. The medicine doesn’t influence serotoninergic system. Bupropion and its active metabolites inhibit norepinephrine and dopamine by means of carrier proteins blockage. The effects on dopamine transporter are taken because of the early start of gene expression c-fos in neurons. Bupropion leads to slowing down of excitement in brain axis and locus coeruleus in parallel with increased concentration of norepinephrine and dopamine in nucleus accumbens. Wellbutrin doesn’t inhibit monoamine oxidase or connect with postsynaptic histamine, serotonin, epinephrine, dopamine, acetyl-cholinergic receptors.

The traditional medicinal form of Wellbutrin requires a three-time prescription per day, the form with slower release requires two-time intake per day, the form with super-long release (bupropion XL) requires 450mg per day. All dosage regimes are bioequivalent.

Bupropion has two active metabolites and each of them has about a one-half activity in comparison with bupropion. Wellbutrin doesn’t metabolize with CYP2 D6 or inhibit this enzyme. It is worth mentioning that combination of bupropion (Wellbutrin) and fluoxetine (Prozac) may cause delirium and convulsionary attack (the mechanism is not clear).

The effectiveness of Wellbutrin is highly competitive with selective serotonin reuptake inhibitors either among out- or in-patients with deep depression: the level of remission achievement in bupropion groups and SSRIs made 47% against 36% in placebo group. In one placebo controlled trial lasting one year, the effectiveness of Wellbutrin in protection against depression setback was observed.

The most frequent adverse drug reactions (met among more than 5% of patients after the intake of 200-400mg of bupropion SR in placebo controlled trials) include headache, vertigo, uncleared bowels, nausea, insomnia. Rash, sickliness and anxiety more often become a reason of refusal to take the medicine any further. In total, a number of patients who have refused therapy in randomized controlled study (due to side-effects as well) is less than 10%. The dosage increase considerably enhances the risk of convulsive disorder development.  In case a medicinal form with slower release is taken, convulsive disorder is met in much the same way as it met while taking SSRIs.

Peculiarity of Wellbutrin lies in a lesser degree of sexual disorders occurrence in comparison with selective serotonin reuptake inhibitors namely Prozac and Celexa. In accordance with one-time research study and pooled analysis it was stated that the level of orgasmic disorders, pathologies of sexual drive on the setting of bupropion were more frequent than after the intake of SSRI and placebo.

Other possible indications to Wellbutrin prescription may be considered:

  • nicotine addiction treatment;
  • hyperkinetic behavior syndrome;
  • attention deficit hyperactivity disorder;
  • obesity.

The efficiency of Wellbutrin in case of anxious disorders was not studied.