MAOIs (phenelzine)

At a glance

Compared with waiting

Large difference compared with waiting, in a combined analysis of 101 trials.

Compared with other treatments

Better than placebo in several US trials. In one trial of 74 people, 64 in 100 responded to phenelzine, compared with 23 in 100 on placebo.

How many get better

In a US trial, about 1 in 4 people were in remission after phenelzine alone at 24 weeks, and about half with phenelzine plus group CBT.

What it takes

Daily tablets, a strict diet, and regular checks with a doctor, including blood pressure.

What they are

MAOIs (monoamine oxidase inhibitors) are an older type of antidepressant. The one tested most for social anxiety is phenelzine. They are effective, but they interact with some foods and many medicines. For that reason, doctors usually consider them only after other treatments have not worked. A doctor decides whether an MAOI is right for you and how to take it safely.

What people report

MAOIs rarely come up in online discussions of social anxiety. Our review of Reddit found no common themes about them. If you want to hear from people who have taken one, ask your doctor about their experience with patients.

What the trials show

• Phenelzine clearly beat placebo. In a US trial of 74 people, 64% responded to phenelzine, compared with 23% on placebo. Most people in the trial had the general form of social anxiety.
• It did as well as group therapy, and worked faster. In a US trial of 133 people, phenelzine and group CBT both beat placebo after 12 weeks. Phenelzine worked faster and did better on some measures.
• Combining helped most. In a later US trial of 128 people, 25.7% were in remission (symptoms below the level of the disorder) at 24 weeks after phenelzine alone. With group CBT alone it was 23.5%, and with placebo 14.8%. With both phenelzine and group CBT, 53.1% were in remission.
• Strong in combined results. A study that combined 101 trials found MAOIs had one of the largest effects compared with waiting. A Cochrane review found people on MAOIs were about 2.4 times as likely to respond as people on placebo.
• Cost-effective. A UK cost study ranked phenelzine among the most cost-effective options, but it did not include the costs of side effects.

Why it is not first choice

MAOIs have fewer and older trials than SSRIs. They also need strict rules about food and other medicines. The UK guideline (NICE) places phenelzine after SSRIs. A related medicine, moclobemide, is used in some countries.

Diet

MAOIs can react with tyramine, a substance found in some foods. The reaction can raise blood pressure dangerously. Your doctor or a dietitian will give you a full list. Foods to be careful with include:

• aged, smoked, fermented, badly stored or spoiled meat, fish, poultry or cheese
• some fruits, vegetables and beans
• fermented yeast products

MedlinePlus also advises avoiding alcohol and caffeine while taking phenelzine. Ask your doctor before having products sweetened with aspartame, such as diet drinks. Details are on the MedlinePlus phenelzine page.

Get emergency help for a severe headache, a slow, fast or pounding heartbeat, chest pain, a stiff neck, sweating with nausea or vomiting, or trouble breathing.

Drug interactions

MAOIs interact with many medicines. Never combine phenelzine with another MAOI. Some supplements, such as tryptophan and tyrosine, can also interact. Phenelzine stays in your body for several weeks after you stop, so the same care applies then.

Before taking any new medicine, supplement or herbal product, check with your doctor or pharmacist. Tell every doctor, dentist and pharmacist that you take an MAOI, or recently stopped one.

Other side effects and stopping

• Phenelzine can cause drowsiness, dizziness, dry mouth, constipation, weight gain and sexual problems. Dizziness is more likely when you stand up quickly.
• Like other antidepressants, they carry a warning about suicidal thoughts in people under 24. If this happens, contact your doctor or a crisis line straight away.
• Do not stop or change the dose without your doctor. Stopping suddenly can cause withdrawal symptoms. Your doctor will usually lower the dose gradually.