1. periodic functional hypothalamic disturbance
The symptoms of primary focal hyperhidrosis are fairly specific. It's called focal or localized because it
only affects specific parts of the body, such as the underarms, groin, head, face, hands, or feet.
Symptoms also tend to be symmetrical, occurring on both sides equally.
Why does it happen? Experts aren't sure, but primary focal hyperhidrosis seems to stem from a minor
malfunction in the nervous system. There's some evidence that it could run in families
Medications can also cause general excessive sweating. Medications that can cause sweating include:
Some psychiatric drugs
Hyperhidrosis with Peripheral Neuropathy
Hyperhidrosis frequently accompanies small-fiber peripheral neuropathies.
Excessive sweating may occur as a compensatory phenomenon involving proximal
regions, such as the head and trunk, that are spared in a dying-back neuropathy. In
addition, patients with small-fiber peripheral neuropathies may have excessive distal
sweating, presumably due to spontaneous firing of injured neurons.[29]
Episodic
hyperhidrosis also occurs commonly in patients with familial dysautonomia (Riley-
Day syndrome), a hereditary sensory and autonomic neuropathy (HSAN III) that
results from a splice defect in the IKBKAPgene on chromosome 9q31.[30]
Hyperhidrosis is classified as primary or secondary, depending on its cause or origin. Primary
hyperhidrosis, also known as essential or idiopathic hyperhidrosis, is caused by an over-active
sympathetic nervous system
Regardless of the type or cause of hyperhidrosis, severe palmar and plantar hyperhidrosis can disrupt
professional and social life and may lead to emotional problems. In the case of secondary hyperhidrosis,
treatment of the underlying condition should first be attempted. In patients with disabling primary
hyperhidrosis, a variety of treatment methods have been used.
The simplest method to control or reduce profuse sweating is the application of topical agents, such as
aluminum chloride or other extra-strength chemical anti-perspirants. Usually recommended as the first
therapeutic measure, topical antiperspirants are effective in cases with light to moderate hyperhidrosis but
have to be repeated regularly. Drysol (aluminum chloride hexahydrate) is a prescription topical anti-
perspirant commonly prescribed for excessive sweating. Drysol is reported to work in 80 % of persons

2. who use it for excessive sweating. Treatment is repeated nightly until sweating is under
control. Thereafter, Drysol is applied once- or twice-weekly or as needed.
The term "paroxysmal sympathetic storms" more appropriately describes what are more likely to
represent a release phenomenon or periodic functional hypothalamic disturbance that may respond
to morphine or bromocryptine.[11]
Oral prescription medications may be prescribed for situational or episodic hyperhidrosis, including anti-
cholinergics (e.g., Robinul, Ditropan), beta-blockers (e.g., atenolol, propanolol), and benzodiazapines
(e.g., Valium, Ativan). Anti-cholinergic medications may be effective for alleviating hyperhidrosis
(ATTRACT, 2002: Altman and Kihiczak, 2002; GP Notebook, 2003). Anti-cholinergics such as
propantheline bromide, glycopyrrolate, oxybutynin, and benztropine are effective because the pre-
glandular neurotransmitter for sweat secretion is acetylcholine (although the sympathetic nervous system
innervates the eccrine sweat glands). Some anti-cholinergics are better tolerated than others. Nyamekye
(2004) stated: "The most effective anticholinergic drug, glycopyrrolate (Robinul and Robinul Forte, Mikart,
Inc., Pharmaceutical Manufacturers, Atlanta, GA) has mild side-effects and is generally well tolerated ....
Topical glycopyrrolate has also been used in the treatment of localised secondary gustatory
sweating." Guidance from the NHS Institute for Innovation and Improvement (CKS, 2009) state that
systemic anticholinergics may have a role before surgery is considered (particularly if the symptoms of
severe). In such circumstances, propantheline bromide is typically used (CKS, 2009; Hornberger et al,
2004). Guidelines from the International Hyperhydrosis Society (IHS, 2008) state that systemic
medications are also indicated in the treatment of generalized hyperhidrosis if treatment of the underlying
condition and medication adjustments fail to reduce sweating.
Table 1. Causes of generalised hyperhidrosis
Endocrine diseases
menopause*
hyperthyroidism*
diabetes**
hypoglycaemia**
pheochromocytoma***
hyperpituitarism***
carcinoid syndrome***
Medications*
propranolol
tricyclic antidepressants
cholinesterase inhibitors
selective serotonin reuptake inhibitors
opioids

3. Febrile infective illness**
malaria
tuberculosis
endocarditis
HIV (seropositive patients)
Congestive heart failure**
Neurological disorders**
Parkinson disease
peripheral neuropathies
brain lesions (eg. malformation of corpus callosum)
Malignancy***
* Uncommon
** Very uncommon
*** Rare
Table 2. Investigations that may be considered for late onset, recent onset or very severe hyperhidrosis
Blood tests
full blood count
electrolytes and renal function tests
liver function tests
thyroid function tests
HIV serology
fasting blood glucose level
Testing for specific infectious diseases as suggested by the history (eg. tuberculosis)
24 hour urinary catecholamines
Table 3. Causes of focal hyperhidrosis
Primary idiopathic hyperhidrosis
Gustatory sweating (sweating after eating or seeing food that produces strong salivation. Chewing can also stimulate sweating)
Neurological causes
spinal injuries
neuropathies

4. Do you find yourself sweating profusely even when the temperature is cool outside? Are you experiencing more
temperature intolerance than normal? If so, you may want to check your medications. There are a surprising
number of medications that cause sweating. Although sweating can be due to a variety of reasons including
medical problems such as hyperthyroidism, panic attacks, low grade fever, and low blood sugar, medications
rank at the top of the list of potential causes of excessive sweating. Which medications are most likely to result
in excessive sweating?
One of the most common drug culprits are the antidepressant group of medications. Most prescription
antidepressants have the potential to cause sweating with up to fifteen percent of people on some brands of
antidepressants experiencing this problem. This seems to be true regardless of the class of antidepressant used.
It's thought that sweating is a result of changes in neurotransmitter levels in the brain such as norepinephrine
which plays a role in the perception of sweating. Sweating with some antidepressants can be so bothersome that
it results in patients discontinuing their medication.
Another class of medications that cause sweating are certain painkillers with a narcotic component such as
synthetic forms of codeine and fentanyl. These drugs can also induce sweating that occurs after bedtime known
as night sweats. Other drugs that cause sweating are certain medications used to treat psychiatric disorders
such as schizophrenia which alter levels of brain neurotransmitters that play a role in the production of
excessive perspiration.
Excessive sweating—diaphoresis—affects up to 22% of patients who take
antidepressants.1
Diaphoresis may interfere with social and occupational activities, which can lead to medication
discontinuation and prevent effective treatment.
Stopping, decreasing, or changing antidepressants are options, but patients may be reluctant if the
current dose has relieved their
depressive symptoms. Adding a medication
to reduce diaphoresis may be appropriate.
Sympathetic division of the peripheral
nervous system signals cholinergic neurons to stimulate sweat gland secretion.
In the CNS, thermoregulation occurs in

5. the hypothalamus through a balanced and
complex interaction among serotonergic
and dopaminergic neurons.1
Consequently,
oral medications to decrease sweating target peripheral or CNS neurons. Although
evidence is limited to case reports, consider cholinergic and serotonergic antagonists
and dopamine partial agonists to relieve
antidepressant-induced diaphoresis.
Pharmacologic options
Peripherally, the anticholinergic agent benztropine reduced or eliminated diaphoresis at doses ranging
from 0.5 mg every
other day to 1 mg/d.2,3 Dry mouth was the
only reported side effect.
Centrally acting serotonin antagonists
may decrease diaphoresis through the
5-HT2A receptor, which signals the hypothalamus to raise body temperature.
Cyproheptadine is an antihistamine with
serotonin receptor antagonism. In case
reports, it reduced or eliminated sweating in doses of 4 mg once or twice daily.4
Mild sedation was the only noted adverse
effect. The norepinephrine and serotonin
antagonist mirtazapine reduced diaphoresis within 2 weeks of initiation at 15 mg/d
with no adverse effects.5
Sweating resolved
after mirtazapine was titrated to 60 mg/d.
In addition to excess serotonin activity,

6. diaphoresis may result from decreased
dopaminergic tone in the hypothalamus.
Centrally acting dopamine agonists—even
partial agonists—may restore homeostasis
and decrease sweating. Aripiprazole, 10 to
20 mg/d, reduced sweating in 2 patients;
no adverse effects were reported.6
Agents to avoid
Antiadrenergic medications such as clonidine have decreased or exacerbated diaphoresis in studies.1
Similarly, paroxetine
may alleviate or cause sweating. It is difficult to attribute paroxetine’s occasional
effectiveness in reducing sweating solely
to its anticholinergic properties because
improvement may be attributed to an initial anxiolytic effect or efficacy in treating
the underlying anxiety disorder.1
References
1. Marcy TR, Britton ML. Antidepressant-induced sweating.
Ann Pharmacother. 2005;39(4):748-752.
2. Pierre JM, Guze BH. Benztropine for venlafaxine-induced
night sweats. J Clin Psychopharmacol. 2000;20(2):269.
3. Garber A, Gregory RJ. Benztropine in the treatment of
venlafaxine-induced sweating. J Clin Psychiatry. 1997;
58(4):176-177.
4. Ashton AK, Weinstein WL. Cyproheptadine for druginduced sweating. Am J Psychiatry. 2002;159(5):
874-875.

7. 5. Buecking A, Vandeleur CL, Khazaal Y, et al. Mirtazapine
in drug-induced excessive sweating. Eur J Clin Pharmacol.
2005;61(7):543-544.
6. Lu BY, Cullen CE, Eide CE, et al. Antidepressant-induced
sweating alleviated by aripiprazole. J Clin Psychopharmacol