Antidepressants are drugs used for the treatment of depression. Despite their name, they are often used to treat a wide range of other conditions, on- or off-label, such as anxiety disorders, obsessive compulsive disorder, eating disorders, chronic pain, neuropathic pain, and some hormone-mediated disorders such as dysmenorrhea, and for snoring, migraines, attention-deficit hyperactivity disorder (ADHD), substance abuse, and occasionally even insomnia or other sleep disorders. They can be used both alone or combination with other medications. Most antidepressants have a delayed onset of action (2–6 weeks) but for those who respond well to a given drug, some degree of efficacy is often seen after one week.
Many off-label or recreational drugs can produce an antidepressant effect, but their use is controversial. Opioids were used to treat major depression until the late 1950s. Amphetamines were used until the mid-1960s. Scant research on the use of opioids limit their use for the treatment of depression, whereas amphetamines have found a thriving market for conditions as widely arrayed as attention deficit disorder, narcolepsy, and obesity, and continue to be studied for myriad applications.
Both opioids and amphetamines induce a therapeutic response very quickly, showing results within twenty-four to forty-eight hours; the therapeutic ratios for both opioids and amphetamines are greater than those of the tricyclic antidepressants. In a small study published in 1995, the opioid buprenorphine was shown to have potential for treating severe, treatment-resistant depression. The nutritional supplement tryptophan is also used in treating some forms of seasonal depression or in combination with use of bright light exposure.
Low dose antipsychotics are also sometimes used, and St John's wort. Benzodiazepines can improve the short-term response of antidepressants when used together, but also carry a risk of physical dependence with reduced effect over time as well as withdrawal symptoms. Antipsychotics can have severe long term negative effects, such as tardive dyskinesia, brain atrophy, and metabolic syndrome Inert placebos can also have significant antidepressant effects.
Non pharmaceutical approaches to the treatment of depression include psychotherapy, cognitive-behavioural therapy, electro-convulsive therapy, acupuncture, exercise, sleep deprivation, or bright light exposure.
Before the 1950s, opioids and amphetamines were commonly used as antidepressants. Their use was later restricted due to their addictive nature and side-effects. Extracts from the herb St John's wort had been used as a "nerve tonic" to alleviate depression.
In 1951, Irving Selikoff and Edward Robitzek, working out of Sea View Hospital on Staten Island, began clinical trials on two new anti-tuberculosis agents developed by Hoffman-LaRoche, isoniazid and iproniazid. Only patients with a poor prognosis were initially treated; nevertheless, their condition improved dramatically. Selikoff and Robitzek noted "a subtle general stimulation... the patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems." The promise of a cure for tuberculosis in the Sea View Hospital trials was excitedly discussed in the mainstream press.
In 1952, learning of the stimulating side-effects of isoniazid, the Cincinnati psychiatrist Max Lurie tried it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved depression in two thirds of their patients and coined the term antidepressant to describe its action. A similar incident took place in Paris, where Jean Delay, head of psychiatry at Sainte-Anne Hospital, heard of this effect from his pulmonology colleagues at Cochin Hospital. In 1952, before Lurie and Salzer, Delay, with the resident Jean-Francois Buisson, reported the positive effect of isoniazid on depressed patients. For reasons unrelated to its efficacy, isoniazid as an antidepressant was soon overshadowed by the more toxic iproniazid, although it remains a mainstay of tuberculosis treatment. The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of diamine oxidase, coupled with a weak inhibition of monoamine oxidase A.
Selikoff and Robitzek also experimented with another anti-tuberculosis, iproniazid; it showed a greater psychostimulant effect, but more pronounced toxicity. Later, Jackson Smith, Gordon Kamman, George Crane, and Frank Ayd, described the psychiatric applications of iproniazid. Ernst Zeller found iproniazid to be a potent monoamine oxidase inhibitor. Nevertheless, iproniazid remained relatively obscure until Nathan Kline, the influential and flamboyant head of research at Rockland State Hospital, began to popularize it in the medical and popular press as a "psychic energizer". Roche put a significant marketing effort behind iproniazid, including promoting its off-label use for depression. Its sales grew until it was recalled in 1961, due to reports of lethal hepatotoxicity.
The antidepressant effect of a tricyclic, a three ringed compound, was first discovered in 1957 by Roland Kuhn in a Swiss psychiatric hospital. Antihistamine derivatives were used to treat surgical shock and later as neuroleptics. Although in 1955 reserpine was shown to be more effective than placebo in alleviating anxious depression, neuroleptics were being developed as sedatives and antipsychotics.
Attempting to improve the effectiveness of chlorpromazine, Kuhn, in conjunction with the Geigy Pharmaceutical Company, discovered that compound "G 22355", later renamed imipramine. Imipramine had a beneficial effect in patients with depression who showed mental and motor retardation. Kuhn described his new compound as a "thymoleptic" "taking hold of the emotions," in contrast with neuroleptics, "taking hold of the nerves" in 1955-56. These gradually became established, resulting in the patent and manufacture in the US in 1951 by Häfliger and SchinderA.
Antidepressants became prescription drugs in the 1950s. It was estimated that no more than 50 to 100 individuals per million suffered from the kind of depression that these new drugs would treat, and pharmaceutical companies were not enthusiastic in marketing for this small market. Sales through the 1960s remained poor compared to the sales of tranquilizers, which were being marketed for different uses. Imipramine remained in common use and numerous successors were introduced. The use of monoamine oxidase inhibitors (MAOI) increased after the development and introduction of "reversible" forms affecting only the MAO-A subtype of inhibitors, making this drug safer to use.
By the 1960s, it was thought that the mode of action of tricyclics was to inhibit norepinephrine reuptake. However, norepinephrine reuptake became associated with stimulating effects. Later tricyclics were thought to affect serotonin as proposed in 1969 by Carlsson and Lindqvist as well as Lapin and Oxenkrug.
Researchers began a process of rational drug design to isolate antihistamine-derived compounds that would selectively target these systems. The first such compound to be patented was zimelidine in 1971, while the first released clinically was indalpine. Fluoxetine was approved for commercial use by the U.S. Food and Drug Administration (FDA) in 1988, becoming the first blockbuster SSRI. Fluoxetine was developed at Eli Lilly and Company in the early 1970s by Bryan Molloy, Klaus Schmiegel, David Wong and others. SSRIs became known as "novel antidepressants" along with other newer drugs such as SNRIs and NRIs with various selective effects.
St John's wort fell out of favor in most countries through the 19th and 20th centuries, except in Germany, where Hypericum extracts were eventually licensed, packaged and prescribed. Small-scale efficacy trials were carried out in the 1970s and 1980s, and attention grew in the 1990s following a meta-analysis. It remains an over-the-counter drug (OTC) supplement in most countries. Research continues to investigate its active component hyperforin and to elucidate its mode of action.
For a more complete list of antidepressants, see
Selective serotonin reuptake inhibitors, SSRIs are thought to prevent the reuptake of serotonin (also known as 5-hydroxytryptamine, or 5-HT) by the presynaptic neuron, thus initially maintaining higher levels of 5-HT in the synapse. Like all anti-depressants their mechanism of action remains unknown.
SSRI antidepressants includes:
Selective norepinephrine reuptake inhibitors (NRIs) inhibit the reuptake of norepinephrine. The NRIs include:
Noradrenergic and specific serotonergic antidepressants NaSSA inhibit reuptake of serotonin, and noradrenaline at the presynaptic alpha-2 adrenergic receptors. Examples include:
Serotonin–norepinephrine reuptake inhibitors (SNRIs) inhibit reuptake of serotonin and norepinephrine. These include:
The Serotonin antagonist and reuptake inhibitors (SARIs) include:
Norepinephrine-dopamine disinhibitors (NDDIs) act by antagonizing the serotonin 5-HT2C receptor, which normally acts to inhibit norepinephrine and dopamine release, thereby promoting outflow of these neurotransmitters.
Tricyclic antidepressants block the reuptake of norepinephrine and serotonin.
The tricyclics include:
Tertiary amine tricyclic antidepressants:
Secondary amine tricyclic antidepressants
Monoamine oxidase inhibitors (MAOIs) inhibit the enzyme monoamine oxidase, which breaks down the neurotransmitters dopamine, serotonin, and norepinephrine. There are two types with regard to the effect on the enzyme, the irreversible and the newer reversible inhibitors. As there are potentially fatal interactions between irreversible MAOIs and certain foods (particularly those containing tyramine), as well as certain drugs, classic irreversible MAOIs are rarely prescribed any more. However, this does not apply to Emsam and moclobemide, Ensam is the transdermal patch form of selegiline, which due to its bypassing of the stomach has a lesser propensity to induce such events, while moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA), which does not require dietary restrictions.
Irreversible monoamine oxidase inhibitors:
Reversible monamine oxidase inhibitors:
Nicotine is believed to act as an antidepressant, by stimulating the release of dopamine and norepinephrine; additionally, nicotine is believed to exert an antidepressant effect due to the desensitisation of nicotinic receptors which occurs as a result of tolerance. Clinical trials have demonstrated nicotine (administered using a dermal nicotine patch) exerts an antidepressant effect in both depressed nonsmokers and smokers, and can be considered for treatment-resistant depression. The proposed mechanism of chronic nicotine causing desensitisation of nicotinic receptors, thereby leading to an antidepressant effect, is consistent with the theory first proposed over 30 years ago and subsequent research that confirmed excessive acetylcholine activity in the brain leads to depressive symptoms. Varenicline, a nicotinic receptor-acting drug used to wean people off of nicotine dependence has also demonstrated antidepressant properties.
Individuals who use caffeine, at moderate doses (fewer than 6 cups of coffee per day), have a reduced incidence of depressive symptoms and an overall reduced risk of suicide. Anxiety is an important side effect of caffeine which occurs more commonly in individuals who suffer from panic disorder or social phobia or when caffeine is taken in excessive amounts.
Other medications are used to "augment" the effect of antidepressants with mixed results. Some of the drugs used include
Psychostimulants such as
Modafinil is unique in its effect on sleep; it increases alertness and reduces drowsiness while the patient is active, but does not inhibit normal sleep. Extreme caution must be used, however, with certain populations. Stimulants are known to trigger manic episodes in people suffering from bipolar disorder. Close supervision of those with substance abuse disorders is urged. Emotionally labile patients should avoid stimulants, as they exacerbate mood shifting. A review article published in 2007 found psychostimulants "may" be effective in treatment-resistant depression with concomitant antidepressant therapy. A more certain conclusion could not be drawn due to substantial deficiencies in the studies available for consideration, and the "somewhat" contradictory nature of their results. However, the authors claim psychostimulants are likely to have a higher level of clinical effectiveness under circumstances in which the patient will probably die soon, so rapid relief is of great importance. In this situation, the patient is likely to die before dependence on, or tolerance of, the medication interferes with their care.
Chronic nicotine intake via nicotine patches results in an increased response to standard antidepressants. Similarly varenicline has been shown to augment subtherapeutic dose levels of SSRIs to produce an antidepressant effect.
Lithium remains the standard treatment for bipolar disorder and is often used in conjunction with other medications. Lithium's potential side effects include thirst, tremors, light-headedness, nausea, diarrhea. Long term use is associated with kidney failure.
Anticonvulsants are also used, particularly in bipolar disorder. They include:
Benzodiazepines also play a prominent role in the treatment of bipolar disorder. The are used to counteract the often nervous or "jittery" effects of psychostimulant medications can produce. For example a common side effect of Prozac is insomnia thus a tranquilizer such as Valium maybe prescribe to offset this effect. Additionally, benzodiazepines have been proven to augment and compliment the effects of antidepressants giving the patient the optimum results of the drug. Due to their potential for dependency however most patients over the course of their treatment take benzodiazepines on an "as needed" (PRN) basis.
The most commonly used benzodiazepines are:
St. John's wort is by far the most widely-used and well-studied herbal antidepressant. A number of other herbs have been used traditionally to treat depression and related ailments like anxiety, but the research on most of these treatments is sparse.
In a small (30-patient), double-blind, randomized clinical trial, saffron (Crocus sativus L.) was to be equally effective with imipramine for treating mild to moderate depression. However, no other researchers have confirmed these results, nor has a larger population study been published. Another small (40-patient), eight-week, double-blind, randomized trial found saffron to have a similar effect to fluoxetine (Prozac) in the treatment of mild to moderate depression, including a similar remission rate and similar rate of side effects. Neither study has been confirmed in larger trials at other centers.
Several plants in the Salvia genus have been studied for antidepressant properties, although most of the research conducted so far has only been from mice and rat studies. Salvia elegans, also known as pineapple sage, is widely used in Mexican traditional medicine, and has been found in single study in mice to have antidepressant and antianxiety properties. Salvia sclarea, also known as clary, is known to have an antidepressant-like effect in rats, which is thought to be explained by modulation of dopamine.
Poor nutrition has been proposed as a risk factor for developing depression. In a study of older adults, poor nutrition was a strong predictor of depressive symptoms.
Omega 3 fatty acids have been proposed as a treatment for depression, alone or in combination with other treatments. One small pilot study of childhood depression (ages six to 12) suggested omega 3 fatty acids may have therapeutic benefits for treating childhood depression. A 2005 review article included double-blind studies, randomized control trials, epidemiological studies linking omega 3 fatty acids consumption and depression found that low fish consumption (the primary source of omega 3 fatty acids) correlated to increased rates of depression, and case-control and cohort studies of unipolar and postpartum depression indicating low blood levels of omega-3 fatty acids in depressed patients.
A 2008 review of clinical studies of the effectiveness of omega-3 fatty acids on depression has shown somewhat inconsistent results: "Of the evaluated studies, 13 showed a significant positive association between omega-3 and depression, while six studies did not show a relationship between the referred variables." To be read with caution because of limited data, a 2008 Cochrane systematic review found in the one eligible study that omega 3 fatty acids are an effective adjunctive therapy for depressed but not manic symptoms in bipolar disorder. The authors found an "acute need" for more randomised, controlled trials.
For depression, the mechanism of action of antidepressants is unknown.
The neurogenic hypothesis states that molecular and cellular mechanisms underlying the regulation of adult neurogenesis is required for remission from depression and that neurogenesis is mediated by the action of antidepressants. Chronic use of antidepressant increased neurogenesis in the hippocampus of rats. Other animal research suggests that long term drug-induced antidepressants effects modulate the expression of genes mediated by clock genes, possibly by regulating the expression of a second set of genes (i.e. clock-controlled genes).
The delayed onset of clinical effects from antidepressants indicates involvement of adaptive changes in antidepressant effects. Rodent studies have consistently shown upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP) system induced by different types of chronic but not acute antidepressant treatment, including serotonin and norepinephrine uptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, lithium and electroconvulsions. cAMP is synthesized from adenosine 5-triphosphate (ATP) by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs).
One manifestation of depression is an altered hypothalamic-pituitary-adrenal axis (HPA axis) that resembles the neuro-endocrine (cortisol) response to stress, that of increased cortisol production and a subsequent impaired negative feedback mechanism. It is not know whether this HPA axis disregulation is reactive or causative for depression. This briefing suggest that the mode of action of antidepressants may be in regulating HPA axis function.
In 1965, Joseph Schildkraut postulated the Monoamine Hypothesis when he posited an association between low levels of neurotransmitters and depression. By 1985, the monoamine hypothesis was mostly dismissed until it was revived with the introduction of SSRIs through the successful direct-to-consumer advertising, often revolving around the claim that SSRIs correct a chemical imbalance caused by a lack of serotonin within the brain.
To date, there is no evidence to support serotonin dysfunction in the pathophysiology of this disorder.
Serotonin levels in human brain is measured indirectly by sampling cerebrospinal fluid for its main metabolite, 5-hydroxyindole-acetic acid, or by measuring the serotonin precursor, tryptophan. In one placebo controlled study funded by the National Institute of Health, tryptophan depletion was achieved, but they did not observe the anticipated depressive response. Similar studies aimed at increasing serotonin levels did not relieve symptoms of depression. At this time, decreased serotonin level in the brain and symptoms of depression have not been linked
Although there is evidence that antidepressants inhibit the reuptake of serotonin, norepinephrine, and to a lesser extent dopamine, the significance of this phenomenon in the amelioration of psychiatric symptoms is not known. Given the low overall response rates of antidepressants, and the poorly understood causes of depression, it is premature to assume a putative mechanism of action of antidepressants.
While MAOIs, TCAs and SSRIs increase serotonin levels, others prevent serotonin from binding to 5-HT2A receptors, suggesting it is too simplistic to say serotonin is a happy hormone. In fact, when the former antidepressants build up in the bloodstream and the serotonin level is increased, it is common for the patient to feel worse for the first weeks of treatment. One explanation of this is that 5-HT2A receptors evolved as a saturation signal (people who use 5-HT2A antagonists often gain weight), telling the animal to stop searching for food, a mate, etc., and to start looking for predators. In a threatening situation it is beneficial for the animal not to feel hungry even if it needs to eat. Stimulation of 5-HT2A receptors will achieve that. But if the threat is long lasting the animal needs to start eating and mating again - the fact that it survived shows that the threat was not so dangerous as the animal felt. So the number of 5-HT2A receptors decreases through a process known as downregulation and the animal goes back to its normal behavior. This suggests that there are two ways to relieve anxiety in humans with serotonergic drugs: by blocking stimulation of 5-HT2A receptors or by overstimulating them until they decrease via tolerance.
A number of antidepressants have been compared below:
The values above are expressed as equilibrium dissociation constants. It should be noted that smaller dissociation constant indicates more efficacy. SERT, NET, and DAT correspond to the abilities of the compounds to inhibit the reuptake of serotonin, norepinephrine, and dopamine, respectively. The other values correspond to their affinity for various receptors. Note that desmethylclomipramine, a metabolite of clomipramine, has a comparably high affinity for the NET as clomipramine has for the SERT.
Recent studies show pro-inflammatory cytokine processes take place during clinical depression, mania and bipolar disorder, and it is possible that symptoms of these conditions are attenuated by the pharmacological effect of antidepressants on the immune system.
Studies also show that the chronic secretion of stress hormones as a result of disease, including somatic infections or autoimmune syndromes, may reduce the effect of neurotransmitters or other receptors in the brain by cell-mediated pro-inflammatory pathways, thereby leading to the dysregulation of neurohormones. SSRIs, SNRIs and tricyclic antidepressants acting on serotonin, norepinephrine and dopamine receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of Interferon-gamma (IFN-gamma) and Interleukin-10 (IL-10), as well as TNF-alpha and Interleukin-6 (IL-6). Antidepressants have also been shown to suppress TH1 upregulation.
Antidepressants, specifically TCAs and SNRIs (or SSRI-NRI combinations), have also shown analgesic properties.
These studies warrant investigation for antidepressants for use in both psychiatric and non-psychiatric illness and that a psycho-neuroimmunological approach may be required for optimal pharmacotherapy. Future antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.
To establish efficacy, an antidepressant must show that it can produce a therapeutic effect for the condition for which it is taken. An antidepressant should be more efficacious than placebo to justify the risk associated with side effects. For depression, the Hamilton Depression Rating Scale (HAM-D) is often used to measure the severity of depression. The maximum score for the 17-item HAM-D questionnaire is 52; the higher the score, the more severe the depression. What constitute a sufficient response to a drug has not been well established, but total remission or virtual elimination of all depression symptoms is the goal, however, remission rates are rarely published. For placebo, the percentage of symptom reduction is approximately 31 to 38%, compared to 46 to 54% for antidepressants.
On the basis of 234 studies, no clinically relevant superiority of one antidepressant over another was detected for the treatment of acute, continuation, and maintenance phases of depression, taking into account age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life.
The largest and most expensive study conducted to date, on the effectiveness of pharmacological treatment for depression, was commissioned by the National Institute of Mental Health. The study was dubbed "The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. The results are summarized here.
There were no statistical or meaningful clinical differences in remission rates, response rates, or times to remission or response among any of the medications compared in this study. These included bupropion sustained release, bupropion, citalopram, lithium, mirtazapine, nortriptyline, sertraline, triiodothyronine, tranylcypromine, venlafaxine extended release.
A 2008 review of randomized controlled trials concluded that symptomatic improvement with SSRIs was greatest by the end of the first week of use, but that some improvement continued for at least 6 weeks.
A 2002 review concluded that there was no evidence that antidepressants reduce the risk of recurrence of depression when their use is terminated. The authors of this review advocated that antidepressants be combined with therapy, and pointed to Interpersonal Psychotherapy (IPT) and Cognitive Behavioral Therapy (CBT).
Some clinical reviews include:
The UK National Institute for Clinical Excellence (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression, because the risk-benefit ratio is poor; that for moderate or severe depression an SSRI is more likely to be tolerated than a tricyclic; and that antidepressants for severe depression should be combined with a psychological treatment such as Cognitive Behavioural Therapy.
The American Psychiatric Association 2000 Practice Guideline for the Treatment of Patients with Major Depressive Disorder indicates that, if preferred by the patient, antidepressant medications may be provided as an initial primary treatment for mild major depressive disorder; antidepressant medications should be provided for moderate to severe major depressive disorder unless electroconvulsive therapy is planned; and a combination of antipsychotic and antidepressant medications or electroconvulsive therapy should be used for psychotic depression. It states that efficacy is generally comparable between classes and within classes and that the initial selection will largely be based on the anticipated side-effects for an individual patient, patient preference, quantity and quality of clinical trial data regarding the medication, and its cost.
Between 30% and 50% of individuals treated with a given antidepressant do not show a response. Even where there has been a robust response, significant continuing depression and dysfunction is common, with relapse rates 3 to 6 times higher in such cases. In addition, antidepressant drugs tend to lose efficacy over the course of treatment. A number of strategies are used in clinical practice to try to overcome these limits and variations. They include switching medication, augmentation, and combination.
The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved following six to eight weeks of treatment with an antidepressant, to switch to an antidepressant in the same class, then to a different class of antidepressant. The remission rate reported by the STAR*D study was 21% using this method.
A 2006 meta-analysis review found wide variation in the findings of prior studies; for patients who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug. However, the more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial. However, a later meta-analysis found no difference between switching to a new drug and staying on the old medication; although 34% of treatment resistant patients responded when switched to the new drug, 40% responded without being switched. Thus, the clinical response to the new drug might be a placebo effect associated with the belief that one is receiving a different medication.
For a partial response, the American Psychiatric Association guidelines suggest augmentation, or adding a drug from a different class. These include: lithium and thyroid augmentation, dopamine agonists, sex steroids, NRI's, glucocorticoid-specific agents, or the newer anticonvulsants The STAR*D project reported a remission rate of 30% with this method.
A combination strategy involves adding an additional antidepressant, usually from different class so as to have effect other mechanisms. Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy. The STAR*D project reported similar remission rates as with augmentation strategy.
Opponents of switching, augmentation and combination argue that treatment may also propel the illness to a malignant and treatment-unresponsive course with iatrogenic psychiatric-like symptoms and treatment resistance or episode acceleration.
The therapeutic effects of antidepressants typically do not continue once the course of medication ends, resulting in a high rate of relapse. A recent meta-analysis of 31 placebo-controlled antidepressant trials, mostly limited to studies covering a period of one year, found that 18% of patients who had responded to an antidepressant relapsed while still taking it, compared to 41% whose antidepressant was switched for a placebo. The American Psychiatric Association guidelines advise four to five months of continuation treatment on an antidepressant following the resolution of symptoms. For patients with a history of depressive episodes, the British Association for Psychopharmacology's 2000 Guidelines for Treating Depressive Disorders with Antidepressants advise remaining on an antidepressant for at least six months and as long as five years or indefinitely.
In a five-year follow up, relapse rates was 23% greater for users greater than one year, but not different for 6 or 12 months users. In addition, gradual loss of therapeutic benefit occurs during the course of treatment. A strategy involving the use of pharmacotherapy in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies.
Another possible problem with antidepressants is the chance of antidepressant-induced mania in patients with bipolar depression or manic depression. Many cases of bipolar depression are very similar to those of unipolar depression. Therefore, the patient can be misdiagnosed with unipolar depression and be given antidepressants. Studies have shown that antidepressant-induced mania can occur in 20-40% of bipolar patients.
A review of antidepressant trials submitted to the U.S. FDA by the industry for drug approval revealed that when a trial was successful, the results of the trial was published 94% of the time, however, when the trial was not found to be more effective than placebo, it was only published 50% of the time. This demonstrated a measure of bias in reporting by industry. Combined, 51% of all studies showed efficacy. The difference in effect between active placebos and several anti-depressants appeared small and strongly affected by publication bias.
Controversy regarding the efficacy of antidepressants has arisen due to studies showing that antidepressants fail to provide significantly greater efficacy than placebo in some studies. A 2002 study claimed that the difference between antidepressants and placebo is close to negligible.
A study published in JAMA demonstrated that the magnitude of the placebo effect in clinical trials of depression have been growing over time, while the effect size of tested drugs has remained relatively constant. The authors suggest that one possible explanation for the growing placebo effect in clinical trials is the inclusion of larger number of participants with shorter term, mild, or spontaneously remitting depression as a result of decreasing stigma associated with antidepressant use.
An article in The Washington Post titled "Against Depression, a Sugar Pill Is Hard to Beat" stated,
"A new analysis has found that in the majority of trials conducted by drug companies in recent decades, sugar pills have done as well as-or better than-antidepressants. Companies have had to conduct numerous trials to get two that show a positive result, which is the Food and Drug Administration's minimum for approval. What's more, the sugar pills, or placebos, cause profound changes in the same areas of the brain affected by the medicines, according to research published last week... the makers of Prozac had to run five trials to obtain two that were positive, and the makers of Paxil and Zoloft had to run even more... When Leuchter compared the brain changes in patients on placebos, he was amazed to find that many of them had changes in the same parts of the brain that are thought to control important facets of mood... Once the trial was over and the patients who had been given placebos were told as much, they quickly deteriorated. People's belief in the power of antidepressants may explain why they do well on placebos..."
Through a Freedom of Information Act request, two psychologists obtained 47 studies used by the FDA for approval of the six antidepressants prescribed most widely between 1987-99. Overall, antidepressant pills worked 18% better than placebos, a statistically significant difference, "but not meaningful for people in clinical settings", says psychologist Irving Kirsch, lead author of the study. He and co-author Thomas Moore released their findings in "Prevention and Treatment", an e-journal of the American Psychological Association. In a later publication, Kirsch concluded that the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance.
Another study by psychologists at the University of Pennsylvania, Vanderbilt University, the University of Colorado, and the University of New Mexico also found that antidepressant drugs hardly have better effects than a placebo in those cases of mild or moderate depression. The study was published in the Journal of the American Medical Association. The study focused on paroxetine (Paxil) from GlaxoSmithKline and imipramine.
The Cochrane Collaboration recently performed a systematic review of clinical trials of the generic antidepressant amitriptyline. The study concluded that in spite of moderate evidence for publication bias, there is strong evidence that the efficacy of amitriptyline is superior to placebo.
A review commissioned by the National Institute for Clinical excellence concluded that there there is strong evidence that SSRIs have greater efficacy than placebo on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression. The treatment guidelines developed in conjunction with this review suggest that antidepressants should be considered in patients with moderate to severe depression and those with mild depression that is persistent or resistant to other treatment modalities.
In 2005, anti-depressants became the most prescribed drug in the United States, causing more debate over the issue. Some doctors believe this is a positive sign that people are finally seeking help for their issues. Others disagree, saying that this shows that people are becoming too dependent on anti-depressants.
In 2012, Aimee Hunter and her team used EEG and showed that taking placebo decreased pre-frontal brain activity in those subjects who had prior use of an antidepressants, similar to the expected antidepressant response, but increased brain activity in antidepressant naive subjects. She attributes this antidepressant response of placebo, in repeat users, to a memory effect.
However, in the later experiment conducted by John H. Krystal at Yale University School of Medicine to assess whether growth mixture modeling can provide insights into antidepressant and placebo responses in clinical trials of patients with major depression showed that Duloxetine and SSRI did not differ in efficacy, and compared with placebo they significantly decreased the odds of following the nonresponder trajectory. Antidepressant responders had significantly better HAM-D scores over time than placebo-treated patients, but antidepressant nonresponders had significantly worse HAM-D scores over time than the placebo-treated patients.
Difficulty tolerating adverse effects is the most common reason for antidepressant discontinuation. Over 1500 side effects have been cataloged for the SSRI alone.
SSRI side effects include but are not limited to: Serotonin syndrome, nausea, diarrhea, increased blood pressure, agitation, headaches, anxiety, nervousness, emotional lability, increased suicidal ideation, suicide attempts, insomnia, drug interactions, neonate adverse reactions, anorexia, dry mouth, somnolence, tremors, sexual dysfunction, decreased libido, asthenia, dyspepsia, dizziness, sweating, personality disorder, epistaxis, urinary frequency, menorrhagia, mania/hypomania, chills, palpitations, taste perversion, and micturition disorder drowsiness, GI irregularities,muscle weakness, long term weight gain.
SSRIs inhibit serotonin-mediated platelet activation. This leads to increased risk of gastrointestinal bleeding; at times as high as 57% increase in risk. This is especially important in the elderly, those with a history of peptic ulcer disease or previous gastrointestinal bleeding, and those on blood thinners, such as aspirin and clopidogrel. A recent observational study shows that SSRIs may increase the risk of transient ischemic attacks and strokes compared with tricyclic antidepressants.
Side-effects of an Noradrenergic and specific serotonergic antidepressant may include drowsiness, increased appetite, and weight gain.
Tricyclic antidepressants common side effects include: dry mouth, blurred vision, drowsiness, dizziness, tremors, sexual problems, skin rash, and weight gain or loss. Toxicity occurs at about ten times normal dosages; these drugs are often lethal in overdoses, as they may cause a fatal arrhythmia. However, tricyclic antidepressants are still used because of their effectiveness, especially in severe cases of major depression, their favorable price, and off label uses.
MAOIs (monoamine oxidase inhibitors) side effects include: MAOI can produce a potentially lethal hypertensive reaction if taken with foods that contain excessively high levels of tyramine, such as mature cheese, cured meats or yeast extracts. Likewise, lethal reactions to both prescription and over the counter medications have occurred. Patients undergoing therapy with MAO inhibiting medications are monitored closely by their prescribing physicians, who are consulted before taking an over the counter or prescribed medication. Such patients must also inform emergency room personnel and keep information with their identification indicating that they are on MAOI. Some doctors suggest the use of medical identification tags. Although these reactions may be lethal, the total number of deaths due to interactions and dietary concerns is comparable to over-the-counter medications.
Other side effects of MAOI include: hepatitis, heart attack, stroke, and seizures. Serotonin syndrome is a side-effect of MAOIs when combined with certain medications. Moclobemide may be preferred in the elderly as its pharmacokinetics are not affected by age, is well tolerated by the elderly as well as younger adults, has few serious adverse events, and, in addition, it is as effective as other antidepressants that have more side-effects; moclobemide also has beneficial effects on cognition. A new generation of MAOIs has been introduced; moclobemide (Manerix), known as a reversible inhibitor of monoamine oxidase A (RIMA), which is as effective as SSRIs and tricyclic antidepressants, in depressive disorders, acts in a more short-lived and selective manner and does not require a special diet.
Breast cancer survivors risk having their disease come back if they use certain antidepressants while also taking the cancer prevention drug tamoxifen, according to research released in May 2009.
Pregnancy can trigger a range of emotions that make it more difficult to cope with depression. The risk of medication discontinuation and relapse have to be weighed against the risk to the developing fetus and baby. Some antidepressants have lower risk for the baby during pregnancy, but the FDA advises for the risk of birth defects with the use of Paxil and the MAOI should be avoided. A neonate may experience a withdrawal syndrome from abrupt discontinuation of the antidepressant at birth. The use of antidepressants during pregnancy is associated with an increased risk of spontaneous abortion, birth defects, and developmental delays. Antidepressants is present in varying amounts in breast milk but the effect on the baby is unknown.
Moreover, SSRIs inhibit nitric oxide synthesis, which leads to vasoconstriction. This is significant in pregnancy as SSRIs have been associated with the development of hypertension and pre-eclampsia of pregnancy. This in turn can lead to fetal prematurity. A 2006 industry based publication in the Journal of the American Medical Association (JAMA) found that discontinuing anti-depressive medication during pregnancy led to more frequent relapse. The JAMA later published a correction noting the financial ties and possible conflict of interest, however, the authors maintained that the ties have no bearing on their research work. Obstetrician and perinatologist Adam Urato told the Wall Street Journal that patients and medical professionals need advice free of industry influence.
Whenever changes in antidepressant dosage occur, whether up or down, a doubling of the risk of suicide is seen. A study of 159,810 users of either amytriptyline, fluoxetine, paroxetine or dothiepin found that the risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days.
The Food and Drug Administration requires Black Box warnings on all SSRIs, which state that they double suicidal rates (from 2 in 1,000 to 4 in 1,000) in children and adolescents. although it's controversial whether this is due to the medication or as part of the depression itself (i.e. efficacious antidepressant effect can cause those that are severely depressed, to the point of severe psychomotor inhibition, are rendered more alert and thus have increased capacity to carry out suicide even though they are relatively improved in state). The increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents.
Young patients should be closely monitored for signs of suicidal ideation or behaviors, especially in the first eight weeks of therapy.
People under the age of 24 who suffer from depression are warned that the use of antidepressants could increase the risk of suicidal thoughts and behaviour. Federal health officials unveiled proposed changes to the labels on antidepressant drugs in December 2006 to warn people of this danger.
The FDA warns against the use of Paxil for children and teens depression in favor of Prozac.
SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents in both the United States with a 14% increase, and 50% increase in the Netherlands.
On September 6, 2007, the Centers for Disease Control and Prevention reported that the suicide rate in American adolescents, (especially girls, 10 to 24 years old), increased 8% (2003 to 2004), the largest jump in 15 years, to 4,599 suicides in Americans ages 10 to 24 in 2004, from 4,232 in 2003, giving a suicide rate of 7.32 per 100,000 people that age. The rate previously dropped to 6.78 per 100,000 in 2003 from 9.48 per 100,000 in 1990.Jon Jureidini, a critic of this study, says that the US "2004 suicide figures were compared simplistically with the previous year, rather than examining the change in trends over several years". The pitfalls of such attempts to infer a trend using just two data points (years 2003 and 2004) are further demonstrated by the fact that, according to the new epidemiological data, the suicide rate in 2005 in children and adolescents actually declined despite the continuing decrease of SSRI prescriptions. "It is risky to draw conclusions from limited ecologic analyses of isolated year-to-year fluctuations in antidepressant prescriptions and suicides.
One promising epidemiological approach involves examining the associations between trends in psychotropic medication use and suicide over time across a large number of small geographic regions. Until the results of more detailed analyses are known, prudence dictates deferring judgment concerning the public health effects of the FDA warnings." Subsequest follow-up studies have supported the hypothesis that antidepressant drugs reduce suicide risk.
Another study was taken the overall rate of suicidal acts was 27 per 1000 person-years, and most events occurred within 6 months of medication initiation. According to this study, no commonly used antidepressant medication has an advantage in regard to suicide-related safety. It remains a question as to whether other therapeutic maneuvers, such as ongoing counseling, provide a protective counter-effect to children's and adolescents' antidepressant-associated risk of suicidal thoughts or behaviour.
Sexual side-effects are also common with SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction. Although usually reversible, these sexual side-effects can, in rare cases, last for months or years after the drug has been completely withdrawn. This is known as Post SSRI Sexual Dysfunction.
In a study of 1022 outpatients, overall sexual dysfunction with all antidepressants averaged 59.1% with SSRIs values between 57 and 73%, mirtazapine 24%, nefazodone 8%, amineptine 7% and moclobemide 4%. Moclobemide, a selective reversible MAO-A inhibitor does not cause sexual dysfunction, and can actually lead to an improvement in all aspects of sexual function.
Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting 5-HT2 and 5-HT3 receptors; decreased dopamine; decreased norepinephrine; blockade of cholinergic and α1 adrenergic receptors; inhibition of nitric oxide synthetase; and elevation of prolactin levels. Mirtazapine is reported to have fewer sexual side-effects, most likely because it antagonizes 5-HT2 and 5-HT3 receptors and may, in some cases, reverse sexual dysfunction induced by SSRIs by the same mechanism.
Bupropion, a dual reuptake inhibitor (NE and DA), often causes a moderate increase in sexual drive, due to increased dopamine activity. This effect is also seen with dopamine reuptake inhibitors, CNS stimulants and dopamine agonists, and is due to increases in testosterone production (due to inhibition of prolactin) and nitric oxide synthesis.
Closely related to sexual side-effects is the phenomenon of emotional blunting, or mood anesthesia. Many users of SSRIs complain of apathy, lack of motivation, emotional numbness, feelings of detachment, and indifference to surroundings. They may describe this as a feeling of "not caring about anything anymore." All SSRIs, SNRIs, and serotonergic TCAs can cause this to varying degrees, especially at high doses.
All major antidepressant drugs, except trimipramine, mirtazapine and nefazodone suppress REM sleep, and it has been proposed that the clinical efficacy of these drugs largely derives from their suppressant effects on REM sleep. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. Mirtazapine either has no effect on REM sleep or increases it slightly. The MAOIs almost completely suppress REM sleep, while the TCAs and SSRIs have been shown to produce immediate (40-85%) and sustained (30-50%) reductions in REM sleep. This effect often causes increased fatigue in patients who take large doses of antidepressants for extended periods of time. Such fatigue can occasionally interfere with a patient's everyday activities. Abrupt discontinuation of MAOIs can cause a temporary phenomenon known as "REM rebound" in which the patient experiences extremely vivid dreams and nightmares.
Many antidepressants (TCA, TecA, paroxetine from the group of SSRI's) are associated with weight gain usually in the range of 5–25 kg (11–55 lb) but rarely upwards of 50 kg (110 lb). The specific cause is unknown, but antidepressants are associated with increased cravings, an inability to feel full despite consuming enough calories, low energy levels and increased daytime sleepiness, which can lead to overeating and a lack of desire to exercise, and dry mouth, which can lead to ingestion of calorie-laden beverages.
The antihistaminic properties of certain TCA and TeCA class antidepressants have been shown to contribute to the common side-effects of increased appetite and weight gain associated with these classes of medication. Eating low fat, low protein carbohydrate snacks and carbohydrate-rich dinners allows the brain to make serotonin, which then controls appetite and balances mood. Carbohydrates thus eaten, as part of a balanced diet, by virtue of their effect on brain serotonin levels, can support weight loss in the setting of antidepressant weight gain.
Withdrawal syndromes have been reported with tricyclic antidepressants, monoamine oxidase inhibitors and with SSRI's. Researchers from the Nordic Cochrane Center in Denmark compared the signs and symptoms of SSRI discontinuation to those of the benzodiazepine withdrawal syndrome and concluded that the withdrawal reactions were so similar that both withdrawal reactions indicated a dependence syndrome. Elsewhere, concerns have been raised that SSRIs cause dependence. Antidepressans may interact with transcription factors known as "clock genes", which may play a role in the addictive properties of drugs (drug abuse), and possibly in obesity. When treatment is prolonged over 6–9 months, processes oppose the initial acute effects of antidepressant drugs (loss of clinical effects). When drug treatment ends, these processes may be unopposed and yield withdrawal symptoms and increased vulnerability to relapse. Such processes are not necessarily reversible. The more antidepressants are switched or potentiated, the more likely oppositional tolerance can take place.
Some of the withdrawal symptoms of SSRI discontinuation include: Anger, anxiety, panic, depression, depersonalization, detachment, confusion, decreased concentration, memory problems, bouts of crying, hallucinations, mania, delirium, headache, sweating, convulsion, myalgias, lethargy, fatigue, sleep disturbances, nightmares, gastrointestinal, balance problems, visual disturbances, electric shock sensations, numbness, parasthesia, restless legs, tingling, tinnitus, tremors, shaking, parkinsonism, aggression, and catatonia.
Moreover, when changes in antidepressant dosage occur, whether up or down, a doubling of the risk of suicide is seen.
To minimize the intensity of withdrawal and rebound effects antidepressants should be discontinued over a period of several weeks or months depending on a person's response to reductions. The Ashton protocol for discontinuation suggest reducing 10% of the remaining dose every week or two Most cases of discontinuation syndrome last between one and four weeks but a substantial minority, perhaps up to 15% of users, have persistent withdrawal symptoms evident one year post-withdrawal. Paroxetine and venlafaxine seem to be particular difficult to discontinue and prolonged withdrawal syndrome lasting over 18 months have been reported with paroxetine. Several peer-support groups help patients to taper off of their antidepressants.
In the United Kingdom, the use of antidepressants increased by 234% in the 10 years up to 2002. In the USA a 2005 independent report stated that 11% of women and 5% of men in the non-institutionalized population (2002) take antidepressants A 1998 survey found that 67% of patients diagnosed with depression were prescribed an antidepressant. A 2007 study suggested that 25% of Americans were overdiagnosed with depression, regardless of any medical intervention. The findings were based on a national survey of 8,098 people.
A 2002 survey found that about 3.5% of all people in France were being prescribed antidepressants, compared to 1.7% in 1992, often for conditions other than depression and often not in line with authorizations or guidelines Between 1996 and 2004 in British Columbia, antidepressant use increased from 3.4% to 7.2% of the population. Data from 1992 to 2001 from the Netherlands indicated an increasing rate of prescriptions of SSRIs, and an increasing duration of treatment. Surveys indicate that antidepressant use, particularly of SSRIs, has increased rapidly in most developed countries, driven by an increased awareness of depression together with the availability and commercial promotion of new antidepressants. Antidepressants are also increasingly used worldwide for non-depressive patients as studies continue to show the potential of immunomodulatory, analgesic and anti-inflammatory properties in antidepressants.
The choice of particular antidepressant is reported to be based, in the absence of research evidence of differences in efficacy, on seeking to avoid certain side-effects, and taking into account comorbid (co-occurring) psychiatric disorders, specific clinical symptoms and prior treatment history.
It is also reported that, despite equivocal evidence of a significant difference in efficacy between older and newer antidepressants, clinicians perceive the newer drugs, including SSRIs and SNRIs, to be more effective than the older drugs (tricyclics and MAOIs). Currently, the most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs), even though a Cochrane systematic review found no major difference in efficacy between SSRIs and tricyclic antidepressants. A survey in the UK found that male general physicians were more likely to prescribe antidepressants than female doctors.
The number of antidepressants prescribed by the NHS in the United Kingdom almost doubled during one decade, authorities reported in 2010. Furthermore the number highly increased in 2009 when 39.1 million prescriptions were issued compared with 20.1 million issued in 1999. Also, physicians issued 3.18 million more prescriptions in 2009 than in 2008. Health authorities believed the increase was partly linked to the recession. However, other reasons include a diagnosis improvement, a reduction of the stigma on mental ill-health, and more distress caused by the economic crisis. Furthermore, physicians concern is that some people who exhibit milder symptoms of depression are being prescribed drugs unnecessarily due to the lack of other options including talking therapies, counseling and cognitive behavior therapy. One more factor that may be increasing the consumption of antidepressants is the fact that these medications now are used for other conditions including social anxiety and post traumatic stress.
The use of antidepressants in the USA doubled over one decade, from 1996 to 2005. Antidepressant drugs were prescribed to 13 million in 1996 and to 27 million people by 2005. In 2008, more than 164 million prescriptions were written. During this period, patients were less likely to undergo psychotherapy.
United States of America: The most commonly prescribed antidepressants in the US retail market in 2010 were:
|Venlafaxine XR||Effexor XR||SNRI||7,603,949|
Germany: The most commonly prescribed antidepressant in Germany is reported to be (concentrated extracts of) Hypericum perforatum (St John's wort).
Netherlands: In the Netherlands, paroxetine, marketed as Seroxat among generic preparations, is the most prescribed antidepressant, followed by the tricyclic antidepressant amitriptyline, citalopram and venlafaxine.
MAOIs can be as effective as tricyclic antidepressants, although they are generally used less frequently because they have a higher incidence of dangerous side effects and interactions.
▪ Premium designs
▪ Designs by country
▪ Designs by U.S. state
▪ Most popular designs
▪ Newest, last added designs
▪ Unique designs
▪ Cheap, budget designs
▪ Design super sale
DESIGNS BY THEME
▪ Accounting, audit designs
▪ Adult, sex designs
▪ African designs
▪ American, U.S. designs
▪ Animals, birds, pets designs
▪ Agricultural, farming designs
▪ Architecture, building designs
▪ Army, navy, military designs
▪ Audio & video designs
▪ Automobiles, car designs
▪ Books, e-book designs
▪ Beauty salon, SPA designs
▪ Black, dark designs
▪ Business, corporate designs
▪ Charity, donation designs
▪ Cinema, movie, film designs
▪ Computer, hardware designs
▪ Celebrity, star fan designs
▪ Children, family designs
▪ Christmas, New Year's designs
▪ Green, St. Patrick designs
▪ Dating, matchmaking designs
▪ Design studio, creative designs
▪ Educational, student designs
▪ Electronics designs
▪ Entertainment, fun designs
▪ Fashion, wear designs
▪ Finance, financial designs
▪ Fishing & hunting designs
▪ Flowers, floral shop designs
▪ Food, nutrition designs
▪ Football, soccer designs
▪ Gambling, casino designs
▪ Games, gaming designs
▪ Gifts, gift designs
▪ Halloween, carnival designs
▪ Hotel, resort designs
▪ Industry, industrial designs
▪ Insurance, insurer designs
▪ Interior, furniture designs
▪ International designs
▪ Internet technology designs
▪ Jewelry, jewellery designs
▪ Job & employment designs
▪ Landscaping, garden designs
▪ Law, juridical, legal designs
▪ Love, romantic designs
▪ Marketing designs
▪ Media, radio, TV designs
▪ Medicine, health care designs
▪ Mortgage, loan designs
▪ Music, musical designs
▪ Night club, dancing designs
▪ Photography, photo designs
▪ Personal, individual designs
▪ Politics, political designs
▪ Real estate, realty designs
▪ Religious, church designs
▪ Restaurant, cafe designs
▪ Retirement, pension designs
▪ Science, scientific designs
▪ Sea, ocean, river designs
▪ Security, protection designs
▪ Social, cultural designs
▪ Spirit, meditational designs
▪ Software designs
▪ Sports, sporting designs
▪ Telecommunication designs
▪ Travel, vacation designs
▪ Transport, logistic designs
▪ Web hosting designs
▪ Wedding, marriage designs
▪ White, light designs
▪ Magento store designs
▪ OpenCart store designs
▪ PrestaShop store designs
▪ CRE Loaded store designs
▪ Jigoshop store designs
▪ VirtueMart store designs
▪ osCommerce store designs
▪ Zen Cart store designs
▪ Flash CMS designs
▪ Joomla CMS designs
▪ Mambo CMS designs
▪ Drupal CMS designs
▪ WordPress blog designs
▪ Forum designs
▪ phpBB forum designs
▪ PHP-Nuke portal designs
ANIMATED WEBSITE DESIGNS
▪ Flash CMS designs
▪ Silverlight animated designs
▪ Silverlight intro designs
▪ Flash animated designs
▪ Flash intro designs
▪ XML Flash designs
▪ Flash 8 animated designs
▪ Dynamic Flash designs
▪ Flash animated photo albums
▪ Dynamic Swish designs
▪ Swish animated designs
▪ jQuery animated designs
▪ WebMatrix Razor designs
▪ HTML 5 designs
▪ Web 2.0 designs
▪ 3-color variation designs
▪ 3D, three-dimensional designs
▪ Artwork, illustrated designs
▪ Clean, simple designs
▪ CSS based website designs
▪ Full design packages
▪ Full ready websites
▪ Portal designs
▪ Stretched, full screen designs
▪ Universal, neutral designs
CORPORATE ID DESIGNS
▪ Corporate identity sets
▪ Logo layouts, logo designs
▪ Logotype sets, logo packs
▪ PowerPoint, PTT designs
▪ Facebook themes
VIDEO, SOUND & MUSIC
▪ Video e-cards
▪ After Effects video intros
▪ Special video effects
▪ Music tracks, music loops
▪ Stock music bank
GRAPHICS & CLIPART
▪ Pro clipart & illustrations, $19/year
▪ 5,000+ icons by subscription
▪ Icons, pictograms
|Custom Logo Design $149 ▪ Web Programming ▪ ID Card Printing ▪ Best Web Hosting ▪ eCommerce Software ▪ Add Your Link|
|© 1996-2013 MAGIA Internet Studio ▪ About ▪ Portfolio ▪ Photo on Demand ▪ Hosting ▪ Advertise ▪ Sitemap ▪ Privacy ▪ Maria Online|